Platinum‐based chemotherapy toxicity severely impedes successful treatment in lung cancer patients. MicroRNAs (miRs) have a significant impact on the occurrence and survival rate of lung cancer. The purpose of this study was to investigate the association between common miRNA variants and platinum‐based chemotherapy toxicity in lung cancer patients. A total of eight functional single nucleotide polymorphisms (SNPs) of miRNA were genotyped in 408 lung cancer patients by MALDI‐TOF mass spectrometry. All the patients were histologically confirmed as lung cancer, and were treated with platinum‐based chemotherapy for at least two cycles. It was found that the polymorphism rs2042553 of miR‐5197 had a significant association with overall severe toxicity in both additive (P=.031, odds ratio [OR]=1.41, 95% confidence interval [CI] 1.03‐1.93) and dominant (P=.009, OR=1.80, 95% CI 1.16‐2.80) models. MiR‐605 rs2043556 was significantly related to severe hepatotoxicity in dominant model (P=.022, OR=2.51, 95% CI 1.12‐4.14). In addition, rs2910164 of miR‐146a had marginal statistical effect on severe hepatotoxicity in additive model (P=.054). The subgroup analyses showed that miR‐27a rs895819 was related to gastrointestinal toxicity in age >56 years old, smoking and non‐smoking patients. Taken together, our results revealed that polymorphisms of miR‐5197, miR‐605, miR‐146a, and miR‐27a contributed to the chemotherapy toxicity of lung cancer, which may serve as a predictive tool for toxicity evaluation of platinum‐based chemotherapy in lung cancer patients.