Autistic traits are highly heritable and characterized by social deficits. Common genetic variants of the autism-related CNTNAP2 gene have been linked with social impairments, but the neural substrates are poorly understood. In the present study, we investigated the genetic effect of common variants of CNTNAP2 (rs2710102 and rs7794745) on gray matter volume and its association with social performance among 442 healthy participants. Our results showed that individuals with rs2710102 GG homozygotes had smaller left superior temporal gyrus (STG)/insular volume than A-allele carriers (AA and AG), while individuals with rs7794745 TT and AT showed smaller right parahippocampal, right STG/insular, and left inferior parietal lobule (IPL) cortex volume than those with rs7794745 AA. Smaller volume of the STG/insular and parahippocampal cortex was associated with poorer social performance. An indirect effect of CNTNAP2 rs7794745 and rs2710102 genotype on the social performance was mediated by the STG/insular cortex and parahippocampal cortex volume. These findings provided insight into the genetic effect of CNTNAP2 variants on social behavior, which may be moderated by the temporal cortex.