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AIM: To investigate the glutathione-S-transferase M1 (GSTM1) polymorphisms in three Chinese minorities,Kazakh, Uygur, and Tajik; and the pathological significance of GSTM1 polymorphisms in esophageal carcinogenesis in Kazakh.METHODS: A total of 1121 blood samples (442 males and 679 females) were obtained from healthy Kazakh (654), Uygur (412) and Tajik (55). Primary esophageal squamous cell cancer (ESCC) tissues from Kazakh were obtained from 116 patients who underwent surgery.GSTM1 polymorphisms were analyzed by a combined approach of PCR and electrophoresis techniques.RESULTS: GSTM1 null genotype was found in 62.63% Uygur, 50.91% Tajik and 47.40% Kazakh. A significantly higher frequency of GSTM1 null genotype in Uygur was observed compared with Kazakh (OR: 1.859, 95% CI: 1.445 -2.391, χ2 = 23.71, P = 0.000). In addition,GSTM1 null genotype was found in 23.53% of welldifferentiated ESCC in Kazakh, in 49.23% of poorly differentiated ESCC, with a significant difference (OR:3.152, 95% CI: 1.403-7.080, χ2 = 8.018, P = 0.007).CONCLUSION: There is a marked difference in the frequency of common GSTM1 null genotype between Uygur and Kazakh. GSTM1 null genotype is associated with differentiation of ESCC in Kazakh.