Abstract: Objective To investigate the relationship between tumor marker and prognosis and metastasis of patients with small cell lung cancer (SCLC) and to evaluate the value of tumor marker forecasting the metastasis. Methods Seventy-three patients with SCLC were retrospectively analyzed. Thirty-eight (52.1%) patients received surgery, and 35 (47.9%) received local radiotherapy. All patients' paraffin-embedded tumor tissues were obtained and the expressions of NSE, GRP, and GRPR were checked by immunohistochemistry. Combined with tumor volumes, the expressions were re-classified and analyzed with progrosis and distant metastasis of patients with small cell lung cancer. Results The positive expression rates of NSE, GRP and GRPR protein in small cell lung cancer were detected as 71.2%, 79.5%, and 75.3%, respectively, of all tumor specimens. The expression of GRP was correlated to that of GRPR significantly (P=0.000). The expression of GRP and GRPR were associated with patients' prognosis and metastasis significantly (P＜0.05). The sensitivity of the expression of GRP and GRPR forecasting the metastasis was both 71.4%, and the specificity of them was 83.9% and 90.3, respectively. Conclusion GRP and GRPR may be an important tumor marker forecasting the invasion and metastasis of small-cell lung cancer.