After a two-year absence, she was reportedly praised for her comic role in the romantic comedy Housefull, which was the fifth highest-grossing Bollywood film of 2010.

[9][10] She was inspired to enter Bollywood after watching Ram Gopal Verma's former protege Urmila Matondkar's movie Rangeela at the age of six.

[11] Khan studied at the Lee Strasberg Theatre and Film Institute in Manhattan, and she quit upon receiving a movie offer.

[13][14][15] In 2004, at the age of 16, Khan was signed to act in Mukesh Bhatt's Tumsa Nahin Dekha but backed out when both she and the director felt the role was too mature for her; she was immediately replaced by Dia Mirza.

Three years later, in 2007, at the age of 18,[16] Khan made her debut in Ram Gopal Verma's controversial romantic thriller Nishabd as Jia where she acted opposite Amitabh Bachchan.

[20] Nonetheless, Khan received a mostly positive reception for her performance, with critics noting her confidence, attitude, and sex appeal.

Raja Sen praised her portrayal of Jia, a seductive, free-spirited teenager, calling her performance "nuanced" and "impressive".

She played Sunita, a medical student who investigates the history of Sanjay Singhania, portrayed by Aamir Khan.

[26] Despite this, Sukanya Verma compliments her performance, commenting that Khan "continues to strike as an exquisite and expressive actress.

That same year, she made her last film appearance in a supporting role as Devika K. Samtani, the ex-wife of Akshay Kumar's character, in Sajid Khan's Housefull with an ensemble cast including Arjun Rampal, Riteish Deshmukh, Deepika Padukone and Lara Dutta.

[29][6][30] Khan had signed a few movies including Udhas Singh's Aap Ka Saaya, in which she was supposed to play Ranbir Kapoor's wife.

[37] On 7 June 2013, a six-page hand-written note was found at her residence by her sister, allegedly addressed to Khan's boyfriend Sooraj Pancholi.

[52][53] The CBI submitted a list of 69 witnesses, including Khan's mother Rabia, the complainant, with the case to begin in March 2018.

[56][57] An episode of the TV series Yeh Hai Aashiqui was loosely based on Jiah Khan's suicide, with Mihika Verma and Rithvik Dhanjani playing the central characters.