The collision happened at 12.35 this afternoon on the northbound lane of the M8 in the townland of Dogstown near Rockwell College.
The driver of the car – a woman in her mid-20s – was pronounced dead at the scene.
Two other women in the car – both in their 50's – have been hospitalised.
One was taken by helicopter to University Hospital Limerick while the other is being treated at South Tipperary General in Clonmel.
The driver of the truck was uninjured.
The M8 is closed northbound between junction10 Cahir and Junction 9 Cashel while forensic collision investigators carry out their work.
Traffic is being diverted off at Junction 10 to the old N8 (R639) via New Inn.
This latest fatality brings to 11 the number of people killed on Tipperary’s roads in 2016.
