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<i>EGFR</i> mutation status is considered as an important predictor of therapeutic responsiveness in non-small-cell lung carcinoma patients. Recent evidence suggests that antioxidant gene polymorphisms are potential predictors of lung cancer risk. Thus, stratification of <i>EGFR</i> mutation-related phenotypes by antioxidant gene polymorphism status can be an effective approach in terms of improving the prognosis of lung cancer patients. The present study was designed to evaluate the distribution frequency of antioxidant gene polymorphisms in lung adenocarcinoma, as well as its association with hotspot <i>EGFR</i> mutations. The study findings revealed that a statistically significant association exists between <i>EGFR</i> L858R mutation and AG + GG genotypes of <i>SOD</i> rs4880 polymorphism. Furthermore, the subgroup analysis data revealed that compared to AA genotype of <i>SOD</i> rs4880, AG + GG genotypes were significantly associated with advanced cancer stage and distant metastasis. Taken together, these findings can be utilized clinically to predict cancer aggressiveness, metastatic, potential and therapeutic responsiveness of lung cancer patients.