Schizophrenia (SZ) is characterized by a variety of complex positive, negative and cognitive symptoms that are differentially expressed in individual patients. Variability in symptom presentation indicates that multiple genes, many involved in neurodevelopment, contribute to the etiology of SZ. The myelin transcription factor 1-like (MYT1L) gene encodes the MYT1L protein that participates in several neurodevelopment pathways. The copy number variant of MYT1L gene is associated with SZ, and single-nucleotide polymorphisms (SNPs) of MYT1L contribute to major depressive disorder. To explore the association of MYT1L polymorphisms with SZ, we examined six SNPs of MYT1L in a Han Chinese population consisting of 528 paranoid schizophrenic patients and 528 healthy subjects. Our results showed that rs17039584 was significantly associated with SZ (A>G), even after Bonferroni correction. When subjects were divided by gender, the rs10190125 allele and genotype remained significantly associated with SZ in female patients. Moreover, we found that rs6742365 was associated with a family history of SZ in females. Other SNPs did not achieve statistical significance for SZ but were associated with individual phenotypes, as measured by the Positive and Negative Syndrome Scale (PANSS) inventory. Our findings suggest that MYT1L may represent a susceptibility gene for SZ in the Han Chinese population and show that a specific SNP may increase susceptibility in females.