Abstract: Objective To understand the etiology of hand foot and mouth disease (HFMD) in Shiyan,Hubei province and provide evidence for the prevention and control of HFMD. Methods A total of 2076 specimens were collected from clinical diagnosed HFMD cases in Shiyan from May 2008 to December 2013,the identification and subtying of the isolates were conducted with one-step RT-PCR or real-time fluorescent quantitative RT-PCR. Descriptive epidemiological analysis was conducted on the etiological detection data of laboratory confirmed HFMD cases. Results Laboratory detection indicated that HFMD was mainly caused by EV71, followed by Cox A16, Cox A6, Cox A10 and other enterovirus from 2008 to 2013,accounting for 46.35% (24.19%-62.23%), 38.12% (13.06%-70.97%), 5.99% (0-13.06%), 3.75% (0-8.28%) and 5.79% (1.37%-15.12%) respectively. All the cases caused by Cox A6 and Cox A10 were children aged 5 years. The incidence peak in summer was during April-June and the incidence sub-peak in winter was during October-November. More than 4 types of pathogens circulated in all counties and districts. The proportion of the cases caused by Cox A6 increased steadily, reaching 13.06% in 2013. Conclusion HFMD epidemic was serious in Shiyam during 2008-2013. The predominant pathogens were EV71 and Cox A16 alternatively. Cox A6 caused cases increased in recent 2 years. It is necessary to pay close attention to the change of pathogen proportion of HFMD in the future prevention and control of HFMD.