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Introduction: Dengue is endemic in more than 100 countries, mainly in tropical and subtropical regions, and the incidence has increased 30-fold in the past 50 years. The situation of dengue in China has become more and more severe, with an unprecedented dengue outbreak hitting south China in 2014. Building a dengue early warning system is therefore urgent and necessary for timely and effective response. Methodology and Principal Findings: In the study we developed a time series Poisson multivariate regression model using imported dengue cases, local minimum temperature and accumulative precipitation to predict the dengue occurrence in four districts of Guangzhou, China. The time series data were decomposed into seasonal, trend and remainder components using a seasonal-trend decomposition procedure based on loess (STL). The time lag of climatic factors included in the model was chosen based on Spearman correlation analysis. Autocorrelation, seasonality and long-term trend were controlled in the model. A best model was selected and validated using Generalized Cross Validation (GCV) score and residual test. The data from March 2006 to December 2012 were used to develop the model while the data from January 2013 to September 2014 were employed to validate the model. Time series Poisson model showed that imported cases in the previous month, minimum temperature in the previous month and accumulative precipitation with three month lags could project the dengue outbreaks occurred in 2013 and 2014 after controlling the autocorrelation, seasonality and long-term trend. Conclusions: Together with the sole transmission vector Aedes albopictus, imported cases, monthly minimum temperature and monthly accumulative precipitation may be used to develop a low-cost effective early warning system. Author Summary: Dengue has emerged as the most important mosquito-borne viral disease globally. With increasing global trade and population movement, the disease is transferred to regions which were previously dengue free. When dengue vector exists and weather factors are suitable, there is the possibility for dengue transmission and even outbreaks happening. Dengue is still believed to be a non-endemic disease in China, with imported cases playing a vital role in local dengue transmission. The situation of dengue is becoming more and more severe with two successive large outbreaks hitting southern China in 2013 and 2014, and the dengue outbreak in 2014 was unprecedented. In this study, we aim to develop a dengue forecasting model that would provide an early warning of dengue outbreak to allow local health authorities and communities to implement timely effective control measures. Our model showed that imported cases in the previous month, monthly minimum temperature in the previous month and monthly accumulative precipitation with three month lags could predict dengue outbreak ahead by one month. We concluded that these variables could be used to develop an early dengue warning model to provide evidence-based decisions for disease control and prevention and including the utilization of limited resources. [ABSTRACT FROM AUTHOR]