Exposure to extreme temperatures or fine particles is associated with adverse health outcomes but their interactive effects remain unclear. We aimed to explore the interactions of extreme temperatures and PM2.5pollution on mortalities. Based on the daily mortality data collected during 2015–2019 in Jiangsu Province, China, we conducted generalized linear models with distributed lag non-linear model to estimate the regional-level effects of cold/hot extremes and PM2.5pollution. The relative excess risk due to interaction (RERI) was evaluated to represent the interaction. The relative risks (RRs) and cumulative relative risks (CRRs) of total and cause-specific mortalities associated with hot extremes were significantly stronger (p< 0.05) than those related to cold extremes across Jiangsu. We identified significantly higher interactions between hot extremes and PM2.5pollution, with the RERI range of 0.00–1.15. The interactions peaked on ischaemic heart disease (RERI = 1.13 [95%CI: 0.85, 1.41]) in middle Jiangsu. For respiratory mortality, RERIs were higher in females and the less educated. The interaction pattern remained consistent when defining the extremes/pollution with different thresholds. This study provides a comprehensive picture of the interactions between extreme temperatures and PM2.5pollution on total and cause-specific mortalities. The projected interactions call for public health actions to face the twin challenges, especially the co-appearance of hot extremes and PM pollution.