This study was aimed to investigate the distribution of CD38 gene 184 locus allele frequency in chronic myeloid leukemia (CML) and its relation with genetic susceptibility of CML. 100 cases of CML were enrolled in patient group; 200 cases of nonhematologic diseases and nontumor diseases were enrolled in control group. The CD38 gene 184 locus polymorphism was detected by PCR-RFLP, the difference of genotypic frequencies in patient and control groups was analyzed by χ(2) test and Fisher exact probability test, the risk of genotype induced leukemia was expressed by odds ratio (OR) and 95% confidence interval (CI). The results showed that the distribution of CD38 gene 184 locus G/G, G/C, C/C genotypes was no significantly different between patients and control groups (p = 0.072). The wild type C/C was used as reference, the distribution of variant G/C genotype frequency in CML group was different statistically from control group (p = 0.032, OR value 0.517, 95%CI 0.283 - 0.947); the C allele frequency was used as reference, the G allele frequency in CML group was higher than that in control group (p = 0.028, OR value 0.597, 95%CI 0.377 - 0.94). It is concluded that the CD38 gene 184 locus G allele may be an protective gene against CML, and reduce the risk of CML relapse.