Hand, foot and mouth disease (HFMD) is a common childhood illness that mainly affects Asian children under the age of 5?years. Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the most common pathogens of HFMD. It is imperative that the susceptible population is screened early and that the severe illness population can be identified via genetic variation detection in children. Four single-nucleotide polymorphisms (SNP) [2'-5'-oligoadenylate synthetase1 (OAS1) rs10774671, selectin P ligand (SELPLG) rs2228315, scavenger receptor class B member 2 (SCARB2) rs41284767 and interleukin 28B (IL28B) rs12979860] were determined by Taqman assays in 333 HFMD samples and 163 control samples. The rs2228315, rs41284767 and rs12979860 polymorphisms did not differ significantly between HFMD patients and the controls, but the prevalence of the rs10774671 polymorphism was significantly different between the control children and children infected with CA16 (GG genotype vs. AA?+?AG genotype, P?