BACKGROUND: Haemorrhagic fever with renal syndrome (HFRS) is climate sensitive. HFRS-weather associations have been investigated by previous studies, but few of them looked into the interaction of meteorological factors on HFRS in different climate zones. OBJECTIVE: We aim to explore the interactions and marginal effects of meteorological factors on HFRS in China. METHODS: HFRS surveillance data and meteorological data were collected from 254 cities during 2006-2016. A monthly time-series study design and generalized estimating equation models were adopted to estimate the interactions and marginal effects of meteorological factors on HFRS in different climate zones of China. RESULTS: Monthly meteorological variables and the number of HFRS cases showed seasonal fluctuations and the patterns varied by climate zone. We found that maximum lagged effects of temperature on HFRS were 1-month in temperate zone, 2-month in warm temperate zone, 3-month in subtropical zone, respectively. There is an interaction effect between mean temperature and precipitation in temperate zone, while in warm temperate zone the interaction effect was found between mean temperature and relative humidity. CONCLUSION: The interaction effects and marginal effects of meteorological factors on HFRS varied from region to region in China. Findings of this study may be helpful for better understanding the roles of meteorological variables in the transmission of HFRS in different climate zones, and provide implications for the development of weather-based HFRS early warning systems.