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Objective: To examine plasma microRNA-21 (miR-21) level in patients with non-small cell lung cancer (NSCLC) and its potential correlation with chemotherapeutic response. Methods: 77 NSCLC patients and 36 age and sex-matched healthy controls were included. Plasma miR-21 concentration was examined using a quantitative real-time reverse transcription polymerase chain reaction assay (qRT-PCR). Potential correlation between plasma mir-21 concentrations with chemotherapeutic responses was analyzed in 35 patients with advanced NSCLC (stages ⅢB and Ⅳ). Results: Plasma miR-21 was significantly higher in NSCLC patients relative to the healthy controls (P＜0.0001). As a biomarker, plasma mir-21 had a receiver operating characteristic (ROC) curve area of 0.729 with 61.04％ sensitivity and 83.33％ specificity. Chemotherapeutic response in the 35 patients with advanced NSCLC (stages ⅢB and Ⅳ)included partial response (PR) (n=11), stable disease and progression disease (SD+PD) (n=24). The overall response rate (CR+PR) was 31.4％. Plasma miR-21 in patients who achieved PR was significantly lower than those who did not respond (SD+PD) (P=0.0487), and comparable to that of the healthy controls (P=0.2744). Conclusion: Plasma miR-21 is a good biomarker for NSCLC, and could be used to predict responses to chemotherapy.