The truck was carrying liquefied natural gas (LNG) when it exploded around 4:45 p.m. on the Shenyang-Haikou Expressway south of Shanghai in Zhejiang province, the official Xinhua News Agency reported.
After the initial blast, a second explosion followed when the damaged truck fell off the expressway onto a factory workshop, local officials told the news agency.
The explosions caused extensive damage to nearby buildings.
Video from state media showed a large explosion and resulting fire.
One photo showed firefighters hosing down a row of buildings with blown-out facades well into the night.
The Wenling city government information office said on its social media account that houses and workshops collapsed and 189 people were treated at six hospitals.
A worker at a nearby restaurant told Xinhua that the blast shattered the windows of her home, but that her mother and brother were unharmed.
Wenling Deputy Mayor Zhu Minglian said more than 2,600 rescue workers were deployed to the site as efforts continue to find any survivors, the BBC reported.
The blast is now under investigation.
China, which has built an extensive national highway network, has seen a rise in vehicle traffic and deadly crashes.
According to the World Health Organization, more than 200,000 people die every year in China in road accidents.
In rural areas, most of those killed are riders of two-wheelers or pedestrians, while in cities, the WHO says that drivers and passengers of cars and E-bike riders are most at risk.
The Associated Press contributed to this report.