The present study aimed to investigate the association of two polymorphisms (rs2844337 and rs11237200) in the P21 protein (cell division control protein 42/Rac)-activated kinase 1 gene with susceptibility to schizophrenia (SCZ) in Chinese Zhuang and Chinese Han populations. A total of 700 patients with SCZ and 700 healthy controls were recruited. Rs2844337 and rs11237200 polymorphisms were genotyped using Sequenom technology. A total of 591 patients completed the Positive and Negative Syndrome Scale (PANSS) assessment. Data were statistically analyzed using PLINK version 1.07 and SPSS version 17.0. In the Chinese Han population, the genotypic (P=0.038) and allelic (P=0.033) frequencies of the 3'-untranslated region (UTR) genetic variation of rs2844337 in patients were significantly decreased compared to that in controls; these frequencies were significantly associated with SCZ susceptibility in the additive model (Padj=0.032) and in the recessive model (Padj=0.031). Moreover, the TG haplotype constructed by rs2844337 and rs11237200 polymorphisms remained significantly associated with SCZ risk following adjustment for gender and age and applying a Bonferroni correction in the Chinese Han population (P-adj=0.003, P-BC=0.009). The adjacent 5'-UTR genetic variation of rs11237200 was significantly associated with the total score (P-adj=0.006), positive scale score (P-adj=0.014) and general psychopathology scale scores (P-adj=0.009) in the recessive model of the Chinese Han population. However, these polymorphisms were not significantly associated with SCZ susceptibility or the PANSS scores in the Chinese Zhuang population. In conclusion, variations in the PAK1 gene influenced the susceptibility and severity of the clinical symptoms of SCZ in the Chinese Han population investigated in the present study.