〔Abstract〕 Objective To explore the predictive value of plasma heat shock protein 90α(HSP90α) and clinicopathologic features on epidermal growth factor receptor(EGFR) gene mutation in patients with non-small cell lung cancer. Methods The data of plasma Hsp90α, gender, clinical stage and the presence of metastasis in 89 newly diagnosed patients of non-small cell lung cancer(NSCLC) were collected, and the predictive value of those data on EGFR gene mutation was retrospectively analyzed. Results The mutation rate of EGFR gene in female, stage ⅢB～Ⅳ and metastasis patients(58.97%, 49.33% and 54.55%) was significantly higher than that in male, stage I～ⅢA and non-metastasis patients(32.00%,14.29% and 13.04%,P<0.05). The level of HSP90α in the EGFR mutant group was higher than that in the wild group(P<0.05). Combined detection of HSP90α, gender, clinical stage and metastasis increased the diagnostic sensitivity of EGFR mutations compared with each indicator alone(P<0.001). Conclusion The level of Plasma HSP90α combined with patients' gender, clinical stage and metastasis has a high clinical value in predicting EGFR mutation, and the combined detection can improve the diagnostic efficacy.