Police said two persons, aged about 60 who were seated in the front seat of the car were killed on the spot,while their two children, aged five and six years, succumbed to injuries in the Government Hospital at Tenkasi.
The three injured are undergoing treatment.
All the victims were travelling in the car and were related to each other, police said.
Police said the occupants of the car were proceeding from Madurai to Courtallam while the lorry was on its way to Madurai from Courtallam.