Background HIV self-testing (HIVST) holds great promise for expanding HIV testing. Nonetheless, large-scale data on HIVST behavior are scant. Millions of HIVST kits are sold through e-commerce platforms each year. Objective This study aims to analyze the spatiotemporal distribution of the HIVST kit–purchasing population (HIVSTKPP) in China. Methods Deidentified transaction data were retrieved from a leading e-commerce platform in China. A joinpoint regression model was used to examine annual trends of the HIVSTKPP rates by calculating average annual percentage change. Bayesian spatiotemporal analysis was performed to locate hot spots with HIVSTKPP rates. Spatial autocorrelation analysis and space-time cluster analysis were conducted to identify clusters of HIVSTKPP. High-high clusters of HIVSTKPP can be identified by spatial autocorrelation analysis, and high-high clusters indicate that a region and its surrounding region jointly had a higher-than-average HIVSTKPP rate. Spatial regression analysis was used to elucidate the association between the number of HIV testing facilities, urbanization ratio (the proportion of urban population in the total population), and gross domestic product per capita and the HIVSTKPP. Results Between January 1, 2016, and December 31, 2019, a total of 2.18 million anonymous persons in China placed 4.15 million orders and purchased 4.51 million HIVST kits on the web. In each of these 4 years, the observed monthly size of the HIVSTKPP peaked in December, the month of World AIDS Day. HIVSTKPP rates per 100,000 population significantly increased from 20.62 in 2016 to 64.82 in 2019 (average annual percentage change=48.2%; P<.001). Hot spots were mainly located in municipalities, provincial capitals, and large cities, whereas high-high clusters and high-demand clusters were predominantly detected in cities along the southeast coast. We found positive correlations between a region’s number of HIV testing facilities, urbanization ratio, and gross domestic product per capita and the HIVSTKPP. Conclusions Our study identified key areas with larger demand for HIVST kits for public health policy makers to reallocate resources and optimize the HIV care continuum. Further research combining spatiotemporal patterns of HIVST with HIV surveillance data is urgently needed to identify potential gaps in current HIV-monitoring practices.