Advani was born in Mumbai. His father is a retired professional who worked in senior management positions with multinationals in the chemical and pharmaceuticals industry and his mother is an advertising professional. His father is Sindhi and mother Maharashtrian.
He studied at Green Lawns High School, Breach Candy, and later did his Masters in chemistry at St. Xavier's College, Mumbai. He married his college sweetheart Suparna Gupta with whom he has a daughter Keya. Advani is the grand nephew of late producer N. N. Sippy and second cousin of actor Tusshar Kapoor and producer Ekta Kapoor.
Assistant director, with Sudhir Mishra's Is Raat Ki Subah Nahin (1996), for which he also co-wrote the screenplay. Subsequently, he worked under Dharma Productions, the production house of the late Yash Johar, father of Karan Johar.
Advani started his career by assisting Saeed and Aziz Mirza in directing Naya Nukkad. Then, he was an assistant director, and assisted Karan Johar in his first two directorial projects, Kuch Kuch Hota Hai (1998) and Kabhi Khushi Kabhi Gham. Advani also had an acting guest appearance in Kuch Kuch Hota Hai, along with Farah Khan during the Neelam Show sequence. . Similarly, he assisted Aditya Chopra on Mohabbatein.
He went on to direct his first film under Dharma Productions, titled Kal Ho Naa Ho starring Shah Rukh Khan, Preity Zinta, Saif Ali Khan and Jaya Bachchan. The film was one of the biggest hits of 2003 and firmly established him as a director. The film won six Filmfare awards.
Advani decided to make his next film and announced that the title of the film would be Salaam-e-Ishq: A Tribute To Love. The film has a huge star cast: Salman Khan, Priyanka Chopra, Sohail Khan, Vidya Balan, John Abraham, Akshaye Khanna, Govinda, Juhi Chawla, Anil Kapoor, Ayesha Takia, Shannon Esra and Anjana Sukhani. The film was produced by Sunil Manchanda, Mukesh Talreja and Chetan Motiwalla and released on 25 January 2007 to mixed reviews.
His next film Chandni Chowk To China, starring Akshay Kumar was released on January 2009, but was a major disappointment. Even though Chandni Chowk To China has disappointed, Nikkhil has announced that he will again work with the film's lead star Akshay Kumar. Patiala House is the title of this film, and it also stars actress Anushka Sharma as the female lead. Shooting began in December 2009, and it was released in 2011. The movie also opened commercially in New York
He has directed India's first stereoscopic 3D animation film, Delhi Safari, which he also wrote the original story. The film was released in October 2012.
After the release of Patiala House in 2011, Nikkhil Advani has partnered with Monisha Advani and Madhu Bhojwani to form Emmay Entertainment, a motion picture production company. Emmay Entertainment first production was D-Day (2013 movie), a film directed by Nikkhil, in association with DAR Motion Pictures, which was released on 19 July 2013.
Nikkhil Advani’s recently released film was Hero, the official remake of Subhash Ghai's directed 1983 film of the same name. It went on floors on 18 February 2014. Hero is Emmay Entertainment’s co-production with Salman Khan Ventures. The film launches Sooraj Pancholi and Athiya Shetty. It also stars Tigmanshu Dhulia, Aditya Pancholi, Sharad Kelkar and Vivaan Bathena. It is released on 11 September 2015. and the recent production release was Katti Batti starring Kangana Ranaut and Imran Khan, a co-production with Disney UTV and being directed by Nikkhil Advani that released on 18 September 2015 (Ganesh Chaturthi weekend).
Emmay Entertainment & Crouching Tiger’s next is Airlift, starring Akshay Kumar and Nimrat Kaur, based on true-life events of the evacuation of 170,000 Indians from Kuwait during the first Gulf War. Airlift is produced by T Series, Cape of Good, Emmay Entertainment and Abundantia Entertainment. Principal photography starts on 21 February 2015 and the film is scheduled to release on 22 January 2016.
Nikkhil Advani's Emmay Entertainment is also producing a new feature film Lucknow Central which is directed by Ranjit Tiwari who has assisted as an associate director to Nikkhil Advani on D-Day (2013 film), Hero (2015 Hindi film), Katti Batti, Guddu Engineer and P.O.W.- Bandi Yuddh Ke. Lucknow Central is said to star Farhan Akhtar as the lead actor.
A TV Film called Shaadi Vaadi And All That, an hour-long film for MTV, produced by Nikkhil Advani is a love triangle with a twist. The show is Kaashvi Nair's directorial debut who worked with Nikkhil as an assistant director.
Nikkhil Advani is also directing a finite TV Series P.O.W.- Bandi Yuddh Ke for Star Plus. The show is an official adaption of an Israeli TV series Hatufim. The series was premieres from 7 November 2016. Several bollywood celebrities have praised the trailer. The show was premiered at MAMI film fest followed by a talk with Gideon Raff.