Aim: To explore relationships between single nucleotide polymorphisms (SNPs) of the CDC25 protein family and the survival and chemotherapy responses of patients with advanced non-small-cell lung cancer (NSCLC). Methods & materials: We genotyped 14 SNPs of the CDC25 family in 663 Chinese patients with advanced NSCLC who were treated with first-line platinum-based chemotherapy and, in evaluable patients, analyzed relationships between the CDC25 family and the efficacy of platinum-based chemotherapy. Results:CDC25A rs3731513 and rs1380053, CDC25C rs6861656, CDC25A haplotype T/A/A/A/C and CDC25C haplotype A/G/G/G/C were significantly associated with the patients' progression-free survival. In addition, CDC25B rs3761218 and haplotype G/T/G/G were associated with the occurrence of severe toxicity with platinum-based chemotherapy, especially gastrointestinal and hematological toxicity. Conclusion: These findings reveal a relationship between genetic variations of the CDC25 family and the efficacy and toxicity of platinum-based chemotherapy in patients with advanced NSCLC, especially in those with non-squamous-cell carcinoma.