Kizilsu Kyrgyz Autonomous Prefecture is an autonomous prefecture in western Xinjiang, China, bordering Kyrgyzstan and Tajikistan. Its capital is Artush. The prefecture is home to 622,222 people (as of 2020^[update]) and covers an area of 70,916 km² (27,381 sq mi). Most Kyrgyz in China reside in Kizilsu; they make up a little over a quarter of the prefecture's population. The Uyghurs are the largest ethnic group in Kizilsu, consisting of nearly two-thirds of the population.

The name Kizilsu (also spelled Kezilesu, derived from Chinese pinyin) refers to the Kezi River and means "red water" in the Turkic languages, which include Kyrgyz and Uyghur. Kiziloy, Kizilto, and the Kizil Caves are nearby places that also use the prefix kizil (red).

Kizilsu was within the territory of the First East Turkestan Republic, which lasted from November 1933 to April 1934. The establishment of the short-lived breakaway state was thanks in part to a political and military alliance between Uyghurs and Kyrgyz in western Xinjiang.

The Southern Xinjiang Administrative Office of the People's Republic of China established the Kizilsu Kyrgyz Autonomous Region on 14 July 1954. The autonomous region was reorganised as an autonomous prefecture in February 1955.

In 1955, the townships of Barin, Jamaterek, and Ujme were transferred from Yengisar County to Akto County, as was Bulungkol from Taxkorgan Tajik Autonomous County of Kashgar Prefecture.

In April 1990, a protest in Barin against Chinese rule in Xinjiang escalated into an armed insurrection, in what came to be known as the Barin uprising or Barin riot.

Kizilsu directly administers 1 county-level city and 3 counties.

According to the 2020 census, Kizilsu has 622,222 inhabitants with a population density of 6.36 inhabitants per km². Most Kyrgyz in China (80 per cent) reside in Kizilsu. As of 2013^[update], 27 per cent of the inhabitants of the prefecture were Kyrgyz.