Schizophrenia (SCZ) is a multifactorial disorder caused by environmental and genetic factors. Studies have shown that various single-nucleotide polymorphisms (SNPs) in the binding sites of microRNAs contribute to the risk of developing SCZ. We aimed to investigate whether the variants located in the 3'-UTR region of LIF (rs929271T>G) and ATF6B (rs8283G>A) were associated with increased susceptibility to SCZ in a population from the south-east of Iran. In this case-control study, a total of 396 subjects were recruited. SNPs were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotyping results showed that the G allele of rs929271 significantly increased the risk of SCZ (OR = 1.58 95%CI = 1.19-2.10, p = 0.001). As for rs929271, the GG genotype of co-dominant (OR = 2.54 95%CI = 1.39-4.64, p = 0.002) and recessive (OR = 2.91 95%CI = 1.77-4.80, p < 0.001) models were strongly linked to SCZ. No significant differences were observed between rs8283 polymorphism and predisposition to SCZ. In silico analyses predicted that rs929271 might alter the binding sites of microRNAs, which was believed to have an unclear role in the development of SCZ. Moreover, rs929271 polymorphism changed the LIF-mRNA folding structure. These findings provide fine pieces of evidence regarding the possible effects of LIF polymorphism in the development of SCZ and regulation of the LIF gene targeted by microRNAs.