Abstract: Objective To analyze the value of neuron-specific enolase (NSE) and pro-gastrin-releasing peptide (proGRP) in the diagnosis and treatment of small cell lung cancer (SCLC). Methods The clinical data of 52 patients with SCLC and 70 patients with non-small cell lung cancer (NSCLC) who were first diagnosed and treated in our hospital from January 2016 to June 2018 were retrospectively analyzed. The serum levels of NSE and proGRP were detected by ELISA and chemiluminescence respectively. Results Before treatment, the serum NSE level in SCLC group was higher than that in NSCLC group (P<0.001), the serum NSE level in ED group was higher than that in LD group (P<0.001), the serum ProGRP level in SCLC group was higher than that in NSCLC group (P<0.001), and the serum ProGRP level in ED group was higher than that in LD group (P<0.001). After 2 cycles of chemotherapy, there were 39 cases in the effective group and 13 cases in the ineffective group. The level of serum NSE in the effective group after treatment was lower than that before treatment, and the difference was statistically significant(P<0.001)|the level of serum NSE in the ineffective group before and after treatment had no statistical significance(P>0.05)|the level of serum ProGRP in the effective group after treatment was lower than that before treatment, and the difference was statistically significant(P<0.001)|the level of serum ProGRP in the ineffective group after treatment was higher than that before treatment, and the difference was statistically significant(P<0.05). Conclusions The elevated levels of serum NSE and ProGRP may be helpful for the differential diagnosis between SCLC patients and NSCLC patients. Serum levels of NSE and ProGRP can be used as an auxiliary basis for SCLC staging. ProGRP may have higher application value than NSE in monitoring the changes of SCLC and evaluating the therapeutic effect.