In a previous study, survivin mRNA expression in non-small cell lung cancer (NSCLC) tissue had been demonstrated to be associated with unfavorable prognosis of patients treated with chemotherapy. In this study, we investigated the survivin mRNA levels in blood of patients with stage IIIA-N2 NSCLC and their association with the efficacy of neoadjuvant chemotherapy (NCT) and disease-free survival (DFS) and overall survival (OS). Blood specimens were collected from 56 patients with stage IIIA-N2 NSCLC before (N0) and after the complete of NCT (N1). Survivin mRNA was measured by real-time quantitative-PCR assay. Receiver operating characteristics curve analysis was undertaken to determine the best cutoff value for survivin mRNA. Results showed that high blood survivin mRNA levels at N0 and N1 were significantly associated with clinical (P = 0.01 and P = 0.008, respectively) and pathologic response (both P = 0.004, respectively). Moreover, the change of blood survivin mRNA levels in these NSCLC patients is associated with the clinical and pathologic response to NCT. Patients with high survivin mRNA levels at N0 and N1 had significantly shorter DFS and OS than those with low survivin mRNA levels (P = 0.021 and P = 0.014, respectively for DFS; P = 0.009 and P = 0.005, respectively for OS). Multivariate analysis demonstrated that high blood survivin mRNA level was an independent predictor for worse DFS and OS in the NSCLC patients receiving NCT. In conclusion, survivin mRNA level in blood from stage IIIA-N2 NSCLC patients receiving NCT is predictive of cancer outcome.