BACKGROUND This study aimed to analyze and explore the relationship between the cytokines IL-4 and IL-10 in relation to gene polymorphism and their respective effects on the susceptibility to virus-induced encephalitis. MATERIAL AND METHODS From January 2012 to June 2013, 112 patients with virus-induced encephalitis (the case group and 109 healthy individuals (the control group) were recruited for the purposes of this study. The functional variations that IL-4 and IL-10 genes exhibit were detected through the use of a function analysis and selection tool for single-nucleotide polymorphisms (FASTSNP). The genotypes of IL-4 were rs2227283 and IL-4 rs2227288, and the genotypes of IL-10 were rs1800871 and IL-10 rs1800872. These genotypes were respectively assessed using direct sequencing. RESULTS IL-4 rs2227283 and IL-10 rs1800871 have no correlation in with risk of virus-induced encephalitis (both P>0.05) GA and AA genotypes were related to IL-4 rs2227288 and GT, while TT and GT + TT genotypes were related to IL-10 rs1800872. These were highlighted as being risk factors in virus-induced encephalitis (all P<0.05). However, the duration of fever, white blood cell (WBC) count, C-reactive protein (CRP), neutrophils, and lymphocytes and monocytes of virus-induced encephalitis patients with IL-4 rs2227288 and IL-10 rs1800872 all displayed significant differences (all P<0.05). Frequencies of GAGT and CAGT haplotypes were evaluated and deemed to be of statistical significance and subsequently were highlighted as being risk factors in virus-induced encephalitis (all P<0.05). CONCLUSIONS IL-4 rs2227288 and IL-10 rs1800872 may contribute to an increased risk for virus-induced encephalitis. Through use of direct sequencing, we showed that genotypes of IL-4 rs2227288 and IL-10 rs1800872 may have particular host susceptibility to virus-induced encephalitis.