The collision occurred around 8 p.m. local time on the Sinan-Jianhe and Jiangkou-Weng’an expressways, in the country’s southwest Guizhou province.
Video from the scene appears to show hundreds of cars and at least one bus stacked into each other.
The pile-up took place on slippery roads amid a drop in temperature following rain in the region.
Much of China has seen snow and ice over recent days, with temperatures hovering around freezing in Guizhou this weekend. The China Meteorological Administration has put a yellow warning of ice on roads into effect.
Ten of the people injured are in hospital and in a critical condition, CGTN says.
Traffic on the expressway has resumed, and Chinese authorities are investigating the incident.