Objective To understand the characteristics of the pathogenchanges in hand, foot and mouth disease (HFMD) in Chuzhou City, so as to guide clinical diagnosis and treatment. Methods In 2012-2016, according to the requirements of Hand, Foot and Mouth Disease Surveillance Program, the sampls of throat swab were randomly collected from 5 patients with HFMD every month in every county (including all severe and dead cases) of Chuzhou City.These samples were detected by RT-PCT for enterovirus nucleic acid detection, including enterovirus EV71, CoxA16 and other enterovirus generic types (PE). Results From 2012 to 2016, 2 475 samples of HFMD cases were collected in Chuzhou City, with a total positive rate of enterovirus nucleic acid 43.35%. The positive rates of EV71, CoxA16 and PE were 41.85%, 27.49% and 30.66%, respectively. There were statistical significance in the different positive rate between 2012 and 2016 (χ²= 77.257,P< 0.001). The lowest positive rate was 27.74% in 2013, and the highest positive rate was 53.05% in 2016. The positive rate showed an upward trend from 2012 to 2016, and the difference was statistically significant by trend chi-square test. (χ²=20.312,P< 0.001).The proportion of EV71 in the total number of positive cases decreased significantly, while the propotion of other enterovirus nucleic acid positive cases increased gradually. The positive rate of enterovirus nucleic acid in HFMD of Dingyuan county (22.58%) and Tianchang City (25.63%) was lower than the average level (43.35%). The positive dectation rate began to increase in April every year, and reached a high point from May to July, and then graduallydecreased. The positive rate of EV71 was higher in May and November. The positive rate of CoxA16 was higher from January to March. The positive rate of PE was higher in December. Conclusion The total positive detection rate of HFMD in Chuzhou was increasing year by year, the main pathogens were other enteroviruses and CoxA16, and the dominant types of pathogens were different in different months. HFMD prevention actions should be taken according to the characteristics of the pathogens.