Combining the comprehensive effects of temperature and humidity, this study applies a heat stress index to project future population exposure to high temperature and related health-risks over China under different climate change scenarios. Results show that the number of high temperature days, population exposure and their related health-risks will increase significantly in the future compared to the reference period (1985–2014), which is mainly caused by the change of >T99p (the wet bulb globe temperature >99th percentile derived from the reference period). The population effect is absolutely dominant in influencing the decrease in exposure to T90-95p (the wet bulb globe temperature is in the range of (90th, 95th]) and T95-99p (the wet bulb globe temperature is in the range of (95th, 99th]), and the climate effect is the most prominent contributor to the upsurge in exposure to > T99p in most areas. An additional 0.1 billion person-days increase in population exposure to T90-95p, T95-99p and >T99p in a given year is associated with the number of deaths by 1002 (95% CI: 570–1434), 2926 (95% CI: 1783–4069) and 2635 (95% CI: 1345–3925), respectively. Compared with the reference period, total exposure to high temperature under the SSP2-4.5 (SSP5-8.5) scenario will increase to 1.92 (2.01) times in the near-term (2021–2050) and 2.16 (2.35) times in the long-term (2071–2100), which will increase the number of people at heat risk by 1.2266 (95% CI: 0.6341–1.8192) [1.3575 (95% CI: 0.6926–2.0223)] and 1.5885 (95% CI: 0.7869–2.3902) [1.8901 (95% CI:0.9230–2.8572)] million, respectively. Significant geographic variations exist in the changes of exposure and related health-risks. The change is greatest in the southwest and south, whereas it is relatively small in the northeast and north. The findings provide several theoretical references for climate change adaptation.