Objective To study the clinical values and relativity of serum levels of NSE and ProGRP (P31-98) in patients with small-cell lung cancer. Methods Serum levels of NSE and ProGRP (31-98) was measured by ELISA in 159 patients with small cell lung cancer(SCLC), 99 patients with benign lung diseases, and 100 healthy subjects, 141 SCLC patients before and after treatment were also measured. Results The medians of NSE and ProGRP (31-98) was 21.33 μg/L and 323.70 pg/ml in patients with SCLC, 4.24 μg/L and 11.94 pg/ml in patients with benign lung diseases, 5.82 μg/L and 8.54 pg/ml in healthy subjects respectively,significantly increased in patients with SCLC as compared to that of the other two groups (P ＜0.01).Given the cut-off levels of 10.35 pg/L for NSE and 47.98 pg/ml for ProGRP(31-98), the sensitivity of diagnosis in SCLC was 71.1% and 88.7 %, respectively.The combination sensitivity and specificity of NSE and ProGRP(31-98)was 95.6 % and 96.8 %. The medians of NSE in SCLC patients with extensive and limited disease was 14.75 μg/L and 34.10 μg/L, the sensitivity was 51.14 % and 93.44 %, respectively; ProGRP (31-98) in the two groups was 143.14 pg/ml and 1061.14 pg/ml, 80.61% and 98.61%, respectively.In SCLC patients with remission after treatment the levels of NSE and ProGRP31-98 was significantly lower than that before treatment, but the levels without remission had no significantly change. There was significant relationship between NSE and ProGRP(31-98) in serum levels of patients with SCLC (r =0.379, P ＜0.01).Conclusion The serum levels of NSE and ProGRP (31-98) in patients are both increased, there are a significant relationship.But ProGRP(31-98) is a more specific and sensitive marker than NSE for the diagnosis of SCLC.The combination of the two markers can improve positive rate and validity.