Abstract: Objective To study the etiology of hand, foot and mouth disease in Shenzhen, Guangdong province, in 2011, and provide laboratory evidence for the prevention and treatment of HFMD. Methods Stool samples were collected from HFMD cases clinically diagnosed in sentinel surveillance hospitals in Shenzhen to detect viral nucleic acid of Enterovirus 71(EV71), Coxakivirus A16(Cox A16) and other enteroviruses by using fluorescent RT-PCR. The amplification of the viral nucleic acid fragments of positive samples were conducted by using RT-nested PCR, then the amplification products sequencing was done. The typing of the viruses was conducted by using Blast software. Results Among 409 HFMD cases,93.64% were under 5 years old, and most of them were aged 1-2 years. The incidence peak occurred during May-September and sub-peak in November. There were 142 EV71 infections(43.83%),53 Cox A16 infections(16.36%) and 129 other enteroviruses infections(39.81%). Among 95 of the 129 other enteroviruses infections,69 were Cox A6 infections(72.63%),12 were Cox A10 infections(12.63%). The remaining cases were Cox A12, Cox A9, Cox A2, Cox A4, Cox B2, Cox B4, ECHO2, ECHO14 and ECHO18 infections. Conclusion The major pathogen of HFMD was EV71 in Shenzhen in 2011, followed by Cox A6 and Cox A16. It is necessary to strengthen the etiological surveillance of HFMD.