Climate change is expected to increase occupational heat stress, which will lead to diminished work performance and labor losses worldwide. However, sub-regional analyses remain insufficient, especially for countries with a heterogeneous spatial distribution of working populations, industries and climates. Here, we projected heat-induced labor losses in China, by considering local climate simulations, working population characteristics and developing an exposure–response function suitable for Chinese workers. We showed that the annual heat-induced work hours lost (WHL), compared to the baseline of 21.3 billion hours, will increase by 121.1% (111.2%–131.1%), 10.8% (8.3%–15.3%), and −17.8% (−15.3%–−20.3%) by the end of the century under RCP(Representative Concentration Pathways)8.5, RCP4.5, and RCP2.6, respectively. We observed an approximately linear upward trend of WHL under RCP8.5, despite the decrease in future working population. Notably, WHL will be most prominent in the southern, eastern and central regions, with Guangdong and Henan accounting for a quarter of national total losses; this is largely due to their higher temperature exposure, larger population size, and higher shares of vulnerable population in total employment. In addition, limiting global warming to 1.5 °C would yield substantial gains. Compared to RCP2.6, RCP4.5, and RCP8.5, all provinces can avoid an average of 11.8%, 33.7%, and 53.9% of annual WHL if the 1.5 °C target is achieved, which is equivalent to avoiding 0.1%, 0.6%, and 1.4% of annual GDP losses in China, respectively. This study revealed climate change will exacerbate future labor losses, and adverse impacts can be minimized by adopting stringent mitigation policies coupled with effective adaptation measures. Policymakers in each province should tailor occupation health protection measures to their circumstances.