Increasing evidence suggests that abnormal synaptic function leads to neuronal developmental disorders and is an important component of the etiology of autism spectrum disorder (ASD). Neurexins are presynaptic cell‐adhesion molecules that affect the function of synapses and mediate the conduction of nerve signals. Thus, neurexins are attractive candidate genes for autism. Since gene families have greater power to reveal genetic association than single genes, we designed this case‐control study to investigate six genetic variants in three neurexin genes (NRXN1, NRXN2, and NRXN3) in a Chinese population including 529 ASD patients and 1,923 healthy controls. We found that two SNPs were significantly associated with ASD after false discovery rate (FDR) adjustment for multiple comparisons. The NRXN2 rs12273892 polymorphism T allele and AT genotype were significantly associated with increased risk of ASD (respectively: OR = 1.328, 95% CI = 1.133–1.557, P < 0.001; OR = 1.528; 95% CI = 1.249–1.868, P < 0.001). The dominant model showed the same association (OR = 1.495, 95% CI = 1.231–1.816, P < 0.001). The NRXN3 rs12879016 polymorphism played a significant role in ASD susceptibility under the dominant model (OR = 0.747, 95% CI= 0.615–0.908, P = 0.023), with the same trend detected for the G allele and GT genotype (respectively: OR = 0.811, 95% CI = 0.699–0.941, P = 0.036; OR = 0.755, 95% CI = 0.615–0.928, P = 0.035). In conclusion, this study supports the importance of two genetic variants in the neurexin gene family in ASD susceptibility in China. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is highly heritable, and studies have found a number of candidate genes that might contribute to ASD. Neurexins are presynaptic cell‐adhesion molecules that affect the function of synapses and mediate the conduction of nerve signals, and they play an important role in normal brain development and become candidate genes for autism. The purpose of our study is to explore the association between variants of the neurexins gene family and ASD in a Chinese population through a case‐control study.