TP53 is one of the major tumor suppressor genes, which is essential for the preservation of genome integrity. Different polymorphic variants of the p53 gene have been demonstrated for their association with several human malignancies. Of these, 16 base pair (bp) duplication in intron 3 of the TP53 gene (PIN3 Ins16bp, rs17878362) is the most extensively studied variant. However, no studies have, so far, investigated the association of this polymorphism with esophageal and gastric cancers. Thus, we aimed to investigate the association of PIN3 Ins16bp polymorphism with esophageal cancer (EC) and gastric cancer (GC) in Kashmir Valley, a northern part of India, where incidence of these cancers is very high. In addition, we also tested other covariates such as smoking/tea consumption as potential confounding factors. We analyzed DNA samples from a total of 243 patients (135 EC and 108 GC patients) and 195 healthy controls for PIN3 Ins16bp polymorphisms using PCR. Data were statistically analyzed using chi-square test and logistic regression models. Results showed that carriers for the PIN3 Ins16bp allele (A2) were associated with increased risk for both EC (OR = 2.31, 95% CI = 1.08-4.97, p = 0.03) and GC (OR = 2.91, 95% CI = 1.28-6.63, p = 0.01). Also, in a recessive model, our results showed that PIN3 Ins16bp A2A2 allele was conferring significant high risk for both EC (OR = 2.18, 95% CI = 1.03-4.59, p = 0.04) and GC (OR = 2.87, 95% CI = 1.29-6.42, p = 0.010). Although smoking (Hukka) and high consumption of salted tea are significant risk factors for both EC and GC, interaction of PIN3 Ins16bp genotypes with these factors did not further modulate the risk of EC and GC. Determination of PIN3 A2A2 genotype may provide a useful genetic marker in predicating high-risk individuals for the development of EC and GC and an early diagnosis.