Objective To explore the application of fuzzy time series model based on fuzzy c-means clustering in forecasting monthly incidence of Hepatitis E in mainland China. Methods Apredictive model (fuzzy time series method based on fuzzy c-means clustering)was developed using Hepatitis E incidence data in mainland China between January 2004 and July 2014. The incidence datafrom August 2014 to November 2014 were used to test the fitness of the predictive model. The forecasting results were compared with those resulted from traditional fuzzy time series models. Results The fuzzy time series model based on fuzzy c-means clustering had 0.001 1 mean squared error (MSE) of fitting and 6.977 5×10-4MSEof forecasting, compared with 0.0017 and 0.0014 from the traditional forecasting model. Conclusion The results indicatethat the fuzzy time series model based on fuzzy c-means clustering has a better performance in forecasting incidence of Hepatitis E.