Abstract <p>Schizophrenia (SCZ) is a highly heritable mental disorder. This study aimed to investigate the clinical significance and potential value of microRNA (miR)-149-5p rs2292832 polymorphism in SCZ patients. In this study, we recruited 239 patients diagnosed with SCZ and 236 healthy individuals as controls. Genotyping was performed using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. The expression levels of miR-149-5p were quantified by RT-qPCR. Allele and genotype frequencies were assessed for Hardy–Weinberg equilibrium. The diagnostic value of miR-149-5p in SCZ patients was evaluated using receiver operating characteristic (ROC) curve analysis. The polymorphism of miR-149-5p rs22928328 may be associated with the risk of developing SCZ. Specifically, carriers of the T allele and the TT genotype were associated with a reduced risk of SCZ. Individuals carrying the CC genotype exhibited the highest proportion of paranoid SCZ, whereas patients with the CT/TT genotypes showed a higher proportion of undifferentiated SCZ compared to those with the CC genotype. The expression of miR-149-5p was significantly upregulated in the SCZ group. In the healthy control group, there was no significant difference in miR-149-5p expression between the two genotypes. However, in the SCZ group, the expression level of miR-149-5p in the CT/TT genotype was significantly lower than that in the CC genotype. The ROC curve analysis indicated that miR-149-5p has a high diagnostic value for SCZ. In conclusion, the polymorphism of miR-149-5p rs2292832 was associated with an increased susceptibility to SCZ.</p>