Our study indicated that multiple SNPs, including rs1381105 (SCN1A), rs2162600 (SCN1A), rs10197716 (SCN2A), rs2119068 (SCN2A), rs2119067 (SCN2A), rs353116 (SCN2A), rs353112 (SCN2A) and rs6740895 (SCN2A), especially the SNP-SNP interaction (rs10197716-rs2119068, rs10197716-rs11889342 and rs7598931-rs12233719) were associated with VPA responsiveness in Chinese Han patients with epilepsy. Here, SCN1A is linked to epilepsy.