Current evidence suggests that apoptosis and the cell cycle system play an important role in cancer development. To identify susceptible genetic markers in these mechanisms, we did an association study in 63 patients and 148 controls. A total of 304 SNPs in 31 gene regions were selected. We evaluated an association at a gene region level by computing the minimum P-value (minP) and doing the false discovery rate (FDR) test. Both SNP and gene-based analyses presented associations with the risk of childhood leukemia for 5 genes: CASP7, CASP14, CASP8AP2, MYC, and RIPK1 (P(trend)<0.05). There were statistically significant associations for CASP7 (rs12416109 and rs3814231, P(trend) = 0.002 and 0.009, respectively, minP = 0.013, FDR = 0.042) and CASP14 (rs8110862, P(trend)<0.001, minP = 0.002, FDR = 0.027). This study suggests that genetic polymorphisms in apoptosis and cell cycle related genes might play a role in childhood leukemia development.