The veteran actor and politician was admitted to Lilavati Hospital after ongoing complaints of feeling weak and fatigued.
He is described as the first Indian "superstar", and has appeared in 163 films since his acting debut in 1966.
Actress Divya Dutta tweeted: "Rip rajesh khanna! t very endearing superstar of indian cinema who brought romance a new meaning on screen!ull b terribly missed kaka ji."
Director Anupam Kher added: "Rajesh Khanna gave us a crash course in Romance. He introduced us to a special twinkle in the eye that made us feel good about ourselves.RIP."
The actor was married to Dimple Kapadia and reportedly proposed to Hema Malini, the mother of Ekta Deol.
Khanna was father-in-law to Akshay Kumar, who married the star's oldest daughter Twinkle Khanna in 2001.
Other Bollywood stars paid tribute to the industry legend who last played a supporting role in 2010's Dilon Ke Khel Mein.
Bipasha Basu told followers: "Loss of a Superstar!Iconic Actor!RIP Rajesh Khanna!"
"Another of Hindi cinema's giants passes, Rajesh Khanna. Our sincere condolences to his family. We will miss him dearly," commented Madhuri Dixit-Nene.
In 2009, Khanna received a Lifetime Achievement Award at the 10th Idea IIFA Awards.