BackgroundIn China, Guangdong and Yunnan are the two most dengue-affected provinces. This study aimed to compare the epidemiological characteristics of dengue fever in Guangdong and Yunnan during 2004–2018.MethodsDescriptive analyses were used to explore the temporal, spatial, and demographic distribution of dengue fever.ResultsOf the 73,761 dengue cases reported in mainland China during 2004–2018, 93.7% indigenous and 65.9% imported cases occurred in Guangdong and Yunnan, respectively. A total of 55,970 and 5938 indigenous cases occurred in 108 Guangdong and 8 Yunnan counties, respectively during 2004–2018. Whereas 1146 and 3050 imported cases occurred in 84 Guangdong and 72 Yunnan counties, respectively during 2004–2018. Guangdong had a much higher average yearly indigenous incidence rate (3.65 (1/100000) vs 0.86 (1/100000)), but a much lower average yearly imported incidence rate (0.07 (1/100000) vs 0.44(1/100000)) compared with Yunnan in 2004–2018. Furthermore, dengue fever occurred more widely in space and more frequently in time in Guangdong. Guangdong and Yunnan had similar seasonal characteristics for dengue fever, but Guangdong had a longer peak period. Most dengue cases were clustered in the south-western border of Yunnan and the Pearl River Delta region in Guangdong. Most of the imported cases (93.9%) in Guangdong and Yunnan were from 9 Southeast Asian countries. Thailand, Cambodia, and Malaysia imported mainly into Guangdong while Myanmar and Laos imported into Yunnan. There was a strong male predominance among imported cases and an almost equal gender distribution among indigenous cases. Most dengue cases occurred in individuals aged 21–50 years, accounting for 57.3% (Guangdong) vs. 62.8% (Yunnan) of indigenous and 83.2% (Guangdong) vs. 62.6% (Yunnan) of imported cases. The associated major occupations (house worker or unemployed, retiree, and businessman, for indigenous cases; and businessman, for imported cases), were similar. However, farmers accounted for a larger proportion of dengue cases in Yunnan.ConclusionsIdentifying the different epidemiological characteristics of dengue fever in Guangdong and Yunnan can be helpful to formulate targeted, strategic plans, and implement effective public health prevention measures in China.