The pile-up took place on a bridge that was shrouded in heavy morning fog, which caused multiple vehicles to crash, according to state-owned The Global Times.
Photos from the scene show the long multi-lane bridge, stretching across fields and the Yellow River, strewn with vehicles crammed into each other.
Cars, cargo trucks, lorries and other vehicles can be seen in the pile-up.
In videos filmed from the ground, the air is still thick with fog.
One clip shows a truck sliding forward, crashing into several smaller cars, as sirens ring in the distance.
Many drivers and passengers were trapped in their cars, according to The Global Times.
Emergency response workers and fire rescuers were deployed to the scene, including personnel from the traffic and health departments.
One eyewitness told The Global Times the pile-up stretched several kilometres long, and that moisture on the bridge made the road particularly slippery.
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In some areas, visibility that morning was only 200 metres, according to Reuters, citing the local meteorology agency.
Several hours after the pile-up, police issued a warning for cars not to cross the bridge due to the fog.
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“In the winter the temperature is low and there is often heavy fog,” traffic police posted on their official account on Weibo, China’s version of Twitter.
It reminded drivers to slow down, use their lights, and to leave dangerous areas as quickly as possible.
The overpass connects Zhengzhou with the city of Xinxiang.
Police shut down the bridge during rescue operations, with traffic resuming later that afternoon.