BackgroundThe aim of this study was to investigate potential associations between CYP2B6 c.516G>T polymorphism and the occurrence and prognosis of acute leukemias (AL) in the Han population of Northwest China.MethodsThe CYP2B6 gene polymorphism was analyzed by PCR‐RFLP and Sanger DNA sequencing in 126 patients with AL and 161 healthy controls.ResultsCompared with controls, there were significantly higher frequencies of GT and TT genotypes and T alleles in AL patients (p < .05), particularly in fusion gene‐positive AL patients. There was no significant difference in CYP2B6 polymorphic genotypes and T alleles between AL patients with complete remission after the first course of chemotherapy and controls (p > .05), while the frequencies in AL patients with partial remission and no remission were significantly higher. The CYP2B6 allele frequency in Han Chinese in Northwest China was significantly different to that reported in Han Chinese and other ethnic minorities in southern China, Uygur Chinese, Vietnamese, African, German, British, Spanish, Turkish, and Argentinian populations; however, there was no significant difference compared with allele frequencies reported in Tibetan and Mongolian Chinese, Japanese, Korean, and American populations.ConclusionOur findings show a strong correlation of the CYP2B6 c.516G>T polymorphism in the Han population of Northwest China with AL, especially fusion gene‐positive AL, and indicate a poor prognosis after the first course of chemotherapy. Our findings also implicate the T allele in AL susceptibility and indicate the existence of racial and geographical differences in allele frequencies of CYP2B6 c.516G>T polymorphism.