Melatonin has an important role in the regulation of human sleep circadian rhythms. Sleep disturbances commonly exist in schizophrenia (SCZ) patients. To begin its performance, melatonin must interact to its receptor. In the present study, Single Nucleotide Polymorphisms (SNPs) of melatonin receptor gene 1 B (MTN1B) with SCZ development in Iranian population were investigated. The current case-control study was performed on 92 SCZ patients and 92 healthy control (HC) subjects. NESTED-PCR and ARMS-PCR modified methods (combination) and ARMSPCR method were used on the genotype. The impact of MTN1B rs3781637 (T/C) and rs10830963(C/G) polymorphism variants on the risk SCZ in the sample of Iranian population was investigated. The findings showed significant association between MTN1B rs10830963(C/G) variant and SCZ (OR=2.78, 95%CI=1.25-6.25, P=0.012, GG vs. CC, OR=1.66, 95%CI=1.09-2.51, P=0.021 G vs. C, OR=3.85 95%CI=.89-8.33, P<0.0001, GG vs. CC+CG). There was no association between MTN1B rs3781637 (T/C) and SCZ risk. In addition, haplotype analysis revealed that TG and CC haplotype of rs3781637 (T/C) and rs10830963 (C/G) polymorphisms were associated with SCZ risk (P=0.039) and protective (P<0.0001) effects, respectively. The findings revealed that MTN1B rs10830963 (C/G) polymorphism was associated with the risk of SCZ; while another SNP rs3781637 (T/C) MTN1B gene did not show any risk/protection association with SCZ. Further studies with larger sample sizes and different ethnicities are required to approve the results.