ObjectivesThe prevention and control of dengue fever (DF) has been a major public health issue in Guangdong (GD) province, China. This study aims to analyze the return period (RP) and the return level (RL) of DF epidemic in GD, to help the formulation of prevention and control plan. MethodsThree models, namely Lognormal distribution (Lognor D.), normal distribution (Norm D.), and generalized logistic distribution (GLD) were selected to fit the annual number of indigenous DF cases in GD from 1978 to 2021. The coefficient of determination (R2), the root mean squared error (RMSE), and the Akaike information criterion (AIC) were used to evaluate the goodness of fit. We predicted the RP of 45130 historical maximum cases that occurred in 2014 and the RP of 4884 peak cases that occurred in 2019 over the 5 years up to 2021. ResultsFitting through the three models, the R2 was 0.98, 0.98, and 0.96, respectively. The predicted RLs of the annual DF case number were between 297 and 43234, 297 and 43233, 362 and 41868 for the RPs of 2–45 years. The predicted RPs of DF outbreaks exceeding the historical maximum were 43, 43, and 44 years, and the RPs of DF epidemic exceeding the peak in 2019 were 7, 7, and 8 years, respectively. Therefore, we predicted that GD would experience a DF outbreak beyond the historical maximum in the next 35 or 36 years from 2022. And in the next 4 or 5 years from 2022, there would be a DF epidemic exceeding the peak in 2019. ConclusionsThe study discloses a temporal periodicity inherent to the DF epidemic in GD. The three models are applicable for forecasting and evaluating the RP and RL of DF epidemic in GD, separately.