This study aims to evaluate the association of serum neuron-specific enolase (NSE) levels with the prognosis of small cell lung cancer (SCLC). Literature retrieval, trials selection and assessment, data collection, and statistical analysis were performed according to the Revman 5.0 guidelines. Literature-based searching was guided to gather data and either fixed-effect or random-effect model was used to pool the hazard ratio (HR) according to the test of heterogeneity. A total of 11 eligible studies that included 3,497 SCLC patients and 3,344 control subjects were analyzed. About 68.6 % of patients had high serum levels of NSE, according to the cutoff value defined by the authors. The HR of high levels of NSE for overall survival (OS) was 1.74 times that of low levels of NSE in SCLC patients (95 % CI, 1.14 to 2.65; P = 0.01). Patients with high levels of NSE appear to have a poorer OS compared with those with low levels of NSE.