Background and purpose:Methylene tetrahydrofolate reductase (MTHFR) plays an important role in metabolism of folate and DNA methylation. This study aimed to investigate the relationship between methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism and chemotherapy side effects in advanced non-small cell lung cancer (NSCLC) patients. Methods:A total of 100 patients with advanced NSCLC conifrmed by pathology were included into this study in Zhejiang Cancer Hospital from Jun. 2007 to May. 2009. All patients received the combined chemotherapy of platinum drug and gemcitabine. MTHFR genotypes were determined by allele-specific-PCR technology. Results:In the 100 cases, genotype frequency of MTHFR C677T T/T, T/C and C/C were 20%, 44%and 36%, respectively. Compared with patients of T/T and T/C genotype, patients of C/C genotype were correlated with decreased rate of thrombocytopenia to chemotherapy (P=0.039). No signiifcant differences were observed concerning gastrointestinal toxicity. Conclusion:MTHFR C677T gene polymorphism can be used to predict the adverse reactions to platinum-based chemotherapy in patients with advanced NSCLC.