Abstract: Objective To understand the molecular epidemiological characteristics of coxsackievirus A6(Cox A6), A4(Cox A4) and A10(Cox A10) isolated from hand foot and mouth disease (HFMD) cases in Guangzhou. Methods Clinical samples were collected from suspected HFMD cases from 2010 to 2015. The RNA detections of Cox A6, A4 and A10 was conducted by using real-time PCR, and the partial VP1 genes of the viruses were sequenced. The homology comparison and phylogenetic analysis of the isolates were performed. The epidemiological characteristics of HFMD caused by different enteroviruses were analyzed. Results Among 12 054 clinical samples collected, 8945 were enterovirus positive, including 2174 Cox A6 samples (24.30%), 144 Cox A4 samples (1.61%) and 155 Cox A10 samples (1.73%).HFMD mainly occurred during April-October. The infection rates of Cox A6 and Cox A10 were highest in age group 1-2 years (30.82%, 23.23%), while the infection rate of Cox A4 was highest in age group 3-4 years (27.78%). More cases occurred in males than in females. Phylogenetic analysis showed that Cox A6, A4 and A10 isolated in Guangzhou shared high homology with the enterovirus strains isolated in other areas in China. Conclusion The major pathogens causing HFMD were EV71, Cox A16 and Cox A6 in Guangzhou, which co-circulated or alternatively circulated. Cox A4 and Cox A10 were also the important pathogen causing HFMD. Long-term surveillance and research of HFMD incidence trend should be strengthened for the prevention and control of HFMD.