Background: In recent years, numerous studies have focused their attention on genes that are part of the insulin/insulin-like growth factor 1 signaling pathway, such as the insulin receptor (INSR) and the insulin receptor substrate 1 (IRS1) genes. Aim: We aimed to examine the association of INSR H1085H C > T and IRS1 G972R polymorphisms with prostate cancer (PC). We also aimed to examine possible association with cancer severity assessed by Gleason score. Materials and methods: We have studied 180 consecutive patients referred for PC screening. The genotyping of two polymorphisms (INSR H1085H C > T and IRS1 G972R) was performed by the polymerase chain reaction-restriction fragment length polymorphism method. Results: There was no difference in genotype (p = 0.794) or allelic (p = 0.621) frequency of the IRS1 G972R polymorphism between PC (n = 119) and control (n 61) groups. However, a significant difference was found in INSR H1085H C > T polymorphism genotype and allelic distribution. Carriers of the polymorphic allele (C/T + T/T) were more frequent in control group patients than in the PC group (54.10% vs. 37.82%; p = 0.040; odds ratio [95% confidence interval] = 0.52 [0.28-0.96]). The IRS1 and INSR polymorphism distribution did not differ in subgroups according to Gleason score. Conclusion: INSR H1085H C > T polymorphism seems to be associated with PC risk, whereas IRS1 G972R is not. However, because of the limited power of this study, there is a possibility that some modest effects of the IRS1 G972R polymorphism on PC risk went undetected. Neither polymorphism is associated with the degree of PC malignancy.