Association of P53 polymorphisms with the increased risk of various cancers has been investigated in numerous studies. However, the results were conflicting and no polymorphism has been determined as a definite risk factor. It is likely that the study of P53 combined genotypes and haplotypes may be more useful than individual polymorphisms. Thus, in this study, we analyzed the associations of intron 3 Ins16bp and exon 4 Arg72Pro polymorphisms, as well as their combined genotypes and haplotypes with the risk of differentiated thyroid carcinoma in Iranian-Azeri patients. This case-control study was performed on 84 Iranian Azeri patients with differentiated thyroid carcinoma and 150 healthy subjects. Intron 3 genotype was determined using PCR products analysis on polyacrylamide gels and AS-PCR was used for genotyping Arg72Pro polymorphism. The javastat online statistics package software and SHEsis program were applied for data analysis. There was no significant difference in genotype frequencies of both two polymorphisms between cases and controls. However, the (-16 ins/-16 ins) (Arg/Pro) genotype combination had a noticeable but not significant association with decreased risk of thyroid cancer development (OR = 0.497 95%CI: 0.209-1.168 P = 0.080) and also the frequency of (-16 ins-Pro) haplotype was significantly higher in controls rather than patients (OR = 0.543 95%CI: 0.326-0.903 P = 0.018). In our study, there was association between (-16 ins-Pro) haplotype with decreased risk of differentiated thyroid carcinoma development in Iranian-Azeri patients.