Evidence concerning the health risk of fine and coarse particles is limited in developing Asian countries. The modifying effect between particles and temperature and season also remains unclear. Our study is one of the first to investigate the acute effect of particles size fractions, modifying effects and interannual variations of relative risk in a developing megacity where particulate levels are extraordinarily high compared to other Asian cities. After controlling for potential confounding, the results of a time-series analysis during the period 2005–2009 show that a 10 μg m⁻³ increase in PM_2.5 levels is associated with a 0.65% (95% CI: 0.29–0.80%), 0.63% (95% CI: 0.25–0.83%), and 1.38% (95% CI: 0.51–1.71%) increase in non-accidental mortality, respiratory mortality, and circulatory mortality, respectively, while a 10 μg m⁻³ increase in PM₁₀ is similarly associated with increases of 0.15% (95% CI: 0.04–0.22%), 0.08% (95% CI: 0.01–0.18%), and 0.44% (95% CI: 0.12–0.63%). We did not find a significant effect of PM_2.5–10 on daily mortality outcomes. Our analyses conclude that temperature and particulates, exposures to both of which are expected to increase with climate change, might act together to worsen human health in Beijing, especially in the cool seasons. The level of the estimated percentage increase assume an escalating tendency during the study period, in addition to having a low value in 2008, and after the Olympic Games, the values increased significantly as the temporary atmospheric pollution control measures were terminated mostly.