Objective To analyze the effects of climate factors and mosquito density on dengue epidemic in Foshan, Guangzhou, Shantou, Shenzhen, and Zhuhai in Guangdong province, China. Methods Dengue surveillance data were obtained from the China National Notifiable Infectious Diseases Reporting System. Aedes density data were collected from the Dengue Vector Aedes Surveillance System. A generalized additive model was used to analyze dengue and Aedes density surveillance data from 2005 to 2015. Results The model results indicated that dengue fever showed a significant positive self-regulation effect (F1.96, 10.84=6 588.650,P<0.01). Mosquito density was significantly positively associated with dengue incidence (F2.98, 10.84=21.810,P<0.01). Mean maximum temperature of lag time 0 month showed a significantly positive nonlinear association with dengue incidence (F1.91, 10.84=215.570,P<0.01). Days with precipitation of the previous month exhibited a significantly n-shape effect on dengue incidence (F2.99, 10.84=101.590,P<0.01), which is positively associated with dengue incidence as days with precipitation was below 15 days, but negatively associated above the threshold. Conclusion Temperature and precipitation regulate the risk of dengue epidemic in Guangdong province. They affect the epidemic and outbreak of dengue fever mainly via changing mosquito population density and population dynamics. Overall, dengue incidence significantly increases with the changes in climate.