To explore the changes of neuron specific enolase (NSE) concentration in serum samples of patients with silicosis. In January 2020, 455 cases of silicosis diagnosed in Yantaishan Hospital from January 2018 to December 2019 were collected, and 60 healthy cases and 120 cases of lung cancer were selected as the healthy group and the lung cancer group. The serum levels of NSE were detected by chemical immunofluorescence assay and compared. The serum NSE level of silicosis patients was [(22.88±7.86) ng/ml], higher than that of healthy group [(17.96±4.42) ng/ml] (<0.05) . Serum NSE levels in the first, second and third stage silicosis groups were higher than those in the healthy group (0.05) . The serum NSE level of silicosis patients was lower than that of the small cell lung cancer group (0.05) . The area under curve of silicosis NSE was 0.718 (<0.01) when the cut-off was 17.49 ng/ml, the sensitivity and specificity of NSE was 78% and 57% respectively. The serum NSE level of patients with silicosis is significantly increased, which can be used as an important reference index for the diagnosis and the differential diagnosis of silicosis.