Devnarayan (Alok Nath) takes responsibility of Gopal (Shah Rukh Khan) and Nita (Suman Ranganathan), the children of his deceased friend. Devnarayan gets so involved in their upbringing that he starts neglecting his daughter, Laxmi (Aroona Irani), and her two kids, Radha (Madhuri Dixit) and Prashant (Atul Agnihotri).

Upset by her father's attitude, Laxmi walks out of the house and decides to raise her two kids with sheer hard work and dedication.

Unable to cope with Laxmi's indifference towards him, Devnarayan falls ill and is hospitalised. When Laxmi learns of his illness, she rushes to the hospital to meet her ailing father, but meets with a car accident on the way. Devnarayan takes the responsibility of bringing up Radha and Prashant as well.

Knowing that Gopal loves Radha since childhood, Devnarayan gets them married. Radha's childhood friend Suraj (Salman Khan) is very close to her and keeps calling her for all his problems, which bothers and upsets Gopal a great deal. Things reach such a stage that Gopal decides to divorce Radha and even throws her out of the house.

Does Radha find solace in Suraj's eyes or does she re-unite with Gopal? HUM TUMHARE HAIN SANAM co-stars Aishwarya Rai as Suman, who plays a blind girl.