The present paper aims to investigate the epidemiological and etiological characteristics of hand，foot and mouth disease (HFMD) in Shanghai from 2009 to 2011. The data from the National Notifiable Disease Report System were analyzed. A total of 6 676 clinical samples were collected and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was performed. 257 samples were cultured with RD cells. The complete sequences of VP1-encoding region in several identified human enterovirus 71 (HEV71) strains were analyzed. The results showed that 18 districts/counties had reported HFMD cases; children ≤5 years old were the most susceptible population; the peak of HFMD epidemic was from April to November; HEV71 and coxsackievirus A16 (CA16) were the major pathogens for this epidemic, but the constituent ratio of HEV71 and CA16 was different in different months and regions. Out of 6 676 patients，4 647 cases were positive for enterovirus by real-time RT-PCR, with the overall positive rate of 69.61%. Among them 1 419 were CAl6 (with the positive rate of 21.26%) and 2 592 were HEV7l (with the overall positive rate of 38.83%). 57 HEV71 strains were obtained, with the isolation rate of 22.18％. BLAST sequence analysis showed that all 27 HEV71 strains from 2009 to 2010 were classified into C4a.