Abstract: Objective 　To investigate the association of the C →G single nucleotide polymorphism (SNP) at the 540 position and C →T SNP at the 580 position in the 3′2 unt ranslated region of p16 exon 3 with sus2 ceptibility to esophageal squamous cell carcinoma ( ESCC) and gast ric cardiac adenocarcinoma ( GCA) in a population of high incidence region, Ci county and She county of North China. Methods 　The genotypes of p16 C540 G and C580 T SNPs were detected by polymerase2chain reaction ( PCR)2rest riction f ragment length polymorphism (RFL P) analysis in 503 cancer patient s (265 ESCC and 238 GCA) and 246 healthy cont rols. Results 　The genotype and allelotype dist ribution of the p16 C540 G SNP in ESCC and GCA pa2 tient s was not significantly different f rom that in healthy cont rols (all P values were more than 0. 05) . The genotype and allelotype dist ribution of the p16 C580 T SNP in ESCC and GCA patient s was not sig2 nificantly different f rom that in healthy cont rols (all P values were more than 0. 05), either. When the two p16 SNPs were combined analyzed, the f requencies of 540C/ 580C, 540C/ 580 T, 540 G/ 580C, and 540 G/ 580 T haplotype among ESCC (80. 8 %, 9. 6 %, 8. 7 % and 0. 9 %), GCA (80. 2 %, 9. 2 %, 9. 5 % and 1. 1 %) patient s was not significantly different f rom that in healthy cont rols (80. 1 %, 10. 4 %, 8. 5 % and 1. 0 %) (all P values were above 0. 05) . Conclusion 　The p16 C540Gand C580 T SNPs might not be in2 dependent factors to predict the risk of the development of ESCC and GCA in Ci county and She County.