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Platinum-based chemotherapy is the standard treatment for NSCLC patients with EGFR wild-type, and as alternative to failure to EGFR inhibitors. However, this treatment is aggressive and most patients experience grade 3⿿4 toxicities. ERCC1, ERCC2, ERCC5, XRCC1, MDM2, ABCB1, MTHFR, MTR, SLC19A1, IL6 and IL16 gene polymorphisms may contribute to individual variation in toxicity to chemotherapy. The aim of this study was to evaluate the effect of these polymorphisms on platinum-based chemotherapy in NSCLC patients. A prospective cohorts study was conducted, including 141 NSCLC patients. Polymorphisms were analyzed by PCR Real-Time with Taqman^® probes and sequencing. Patients with ERCC1 C118T-T allele (p = 0.00345; RR = 26.05; CI_95% = 4.33, 515.77) and ERCC2 rs50872-CC genotype (p = 0.00291; RR = 4.06; CI_95% = 1.66, 10.65) had higher risk of general toxicity for platinum …