The epicenter of the shallow 6.4-magnitude earthquake was in Pishan county, about 160 km (100 miles) northwest of the southern city of Hotan, the US Geological Survey said.
"Currently, the earthquake has resulted in three deaths, including a father and son, and more than 20 injuries," China National Emergency Broadcasting (CNEB) said on its website.
According to the China Earthquake Administration, the deaths occurred in Pishan, which has a population of 258,000, mostly Muslim Uighurs, an ethnic minority within China.
The USGS said the earthquake was just 20 kilometers deep, and initially gave the magnitude as 6.1. The China Earthquake Network Center put the magnitude at 6.5.
The initial quake was followed by a series of aftershocks, with the strongest measuring 4.8. Several traditional houses were reported to have collapsed.
China is regularly hit by earthquakes, with the southwestern provinces of Sichuan and Yunnan being particularly prone.
In May 2008, almost 70,000 people in Sichuan were killed by a 7.9 magnitude quake there, while 600 people were killed in a 6.1 magnitude quake in Yunnan last August.
Authorities say they are optimistic that the death toll in Friday's quake would not be high, as the region is relatively sparsely populated.
tj/kms (AFP, Reuters)