Objective To determine the diagnostic value of multi-slice spiral CT scan combined with serum alpha-fetoprotein (AFP) detection for primary liver cancer. Methods 67 patients with primary liver cancer treated in our hospital from March 2017 to August 2018 were selected as the liver cancer group. The clinical data and imaging data of the patients were collected, and the multi-slice spiral CT scan images of primary liver cancer were summarized. 60 patients with chronic hepatitis (chronic hepatitis group) and 60 patients with cirrhosis (cirrhosis group) were selected. The expression levels of serum AFP in each group were measured, and the positive rate of primary liver cancer by different examination methods was calculated. Results The expression level of AFP gradually increased with the severity of the disease (P＜0.001). The positive rates of AFP, CT plain scan, CT enhancement, AFP+CT plain scan CT enhancement for primary liver cancer were 55.22% (37/67), 67.16% (45/67), and 83.58% (56/67), 100% (67/67) respectively. The positive rate of AFP+CT plain scan CT enhancement for primary liver cancer was significantly higher than that of AFP, CT plain scan and CT enhancement examination(P＜0.05). 74 lesions in total were detected in this study, and they mostly distributed in the right posterior lobe of the liver. The diameter of 7 lesions was less than 1cm, the diameter of 28 lesions was 1～3cm, and the diameter of 39 lesions was more than 3cm. The low-density circular or round-like shadows in CT scan was common. The density of lesions in the enhanced scan showed "high-low-low" changes, There were no obvious enhancements for envelope of the 36 lesions. The envelope of the 29 lesions was completely ring-reinforced. Conclusion Multi-slice spiral CT scan combined with serum AFP examination showed a high positive rate for primary liver cancer.