Abstract: Objective To explore the epidemiologic and clinical features of hand, foot and mouth disease (HFMD) caused by Coxsackie virus A16 (CA16) in Suzhou from 2010 to 2014, and analyze the relationship between the SNPs of oligoadenylate synthetase 1 (OAS1) and HFMD caused by CA16 infection. Methods The clinical data of children diagnosed with HFMD caused by CA16 during 2010 and 2014 were collected. The epidemiological characteristics were analyzed. Among them, 167 cases were selected to make comparison of the clinical features with 166 cases of HFMD caused by EV71 infection in the same period. The genotyping of OAS1 rs10774671 was detected by TaqMan probe technique in 167 cases of CA16 infection children, 166 cases of EV71 infection children with HFMD and 163 healthy children. The relationship between polymorphism of gene and infection of CA 16 was analyzed. Results A total of 9 016 children with HFMD were included. CA16 nucleic acid detected to be positive in 762 cases. The detection rate was 8.45%. CA16 infection was most commonly in summer. Children under 5 years old accounted for 94.62% infected. Compared with EV71 infected children, CA16 infected children had shorter fever time, severer oral herpes, ulcer, and rash in hand, foot and hip, lesser nervous system involvement, fewer cases of high lactate dehydrogenase, high C reactive protein, high IgM or IgG, and significant changes in the percentage of CD3+, CD3+CD4+, CD3+CD8+ and CD3－CD19+ (P all < 0.05). The frequency of GG genotype was significantly higher in CA16 infected HFMD children in OAS1 rs10774671 compared with healthy children (P = 0.475). There was no difference in the genotype OAS1 distribution of rs10774571 between common and severe CA16 infected HFMD group (P = 0.475). Conclusion The epidemiology of CA16 infected HFMD disease in Suzhou area was related with age and season. CA16 infected HFMD children have different clinical features and laboratory characteristics.. Children with OAS1 rs10774671 GG genotype were more susceptible to CA16.