Objective To investigate the clinical value of multi-slice spiral CT signs combined with serum tumor markers CYFRA21-1, carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) in the diagnosis of lung cancer. Methods 112 patients with lung cancer treated in our hospital from May 2013 to March 2018 were enrolled in the study, and the clinical data of all patients were retrospectively analyzed. According to the data, all patients were diagnosed as lung cancer after pathological examination. All patients' gender, age, disease, indicators of clinical examination and imaging data were collected to analyze the sensitivity and specificity of different examination methods for the diagnosis of lung cancer. Results The sensitivity rate and specificity rate of multi-slice spiral CT scan combined with serum CYFRA21-1, CEA and NSE for the diagnosis of lung cancer were 90.2% and 94.6%, respectively, which were significantly higher than those of separate examinations, or CT lonely or the combined examination of three indicators (P<0.05). In 112 patients with lung cancer, CT images of 68patients showed lobulated sign,and 72 cases showed spiculation.The lesions can be characterized by irregular high-density shadows, and the mediastinal window shows the density of soft tissue in the plain scan of CT;and the lung lesions are expressed in uneven density and are obviously enhanced in the arterial phase. Mild continuous reinforcement.in the enhanced scan. Conclusion Compared with single CT or detectionof tumor marker, multi-slice spiral CT combined with serum NSE, CYFRA21-1 and CEA detection has higher sensitivity and specificity for the diagnosis of lung cancer, and has more clinical value.