Objective: To investigate and analyze the value of multi-slice spiral CT in differentiating SCLC from NSCLC. Methods: From March 2019 to June 2024, 112 patients with lung cancer diagnosed and treated in our hospital were selected as research objects. All patients were given multi-slice spiral CT phase III enhanced scanning to record CT features and determine diagnostic value. Results: Among the 112 patients, 82 cases of non-small cell lung cancer (NSCLC group) and 30 cases of small cell lung cancer (small cell lung cancer group) were determined by operation and pathology. There was no significant difference in the resolution scores of multi-plane reconstruction and maximum density projection in NSCLC group compared with that in NSCLC group (P>0.05). The proportion of CT features such as vascular aggregation, lobular sign and zigzag sign in NSCLC group was 30.49%, 32.93% and 31.71%, which were lower than 90.00%, 90.00% and 86.67% in NSCLC group, and the difference was statistically significant (P<0.05). However, the proportion of burrs in NSCLC group was higher than that in NSCLC group. The difference was statistically significant (P<0.05). The CT values in the extended stage, venous stage and arterial stage of NSCLC group were significantly different from those in the small cell lung cancer group (P<0.05). There were 81 cases of non-small cell lung cancer diagnosed by multi-slice spiral CT phase III enhanced scan. The sensitivity of multi-slice spiral CT phase III enhanced scan in differentiating non-small cell lung cancer and small cell lung cancer was 97.56%(80/82) and 96.67%(29/30), respectively. The total diagnostic accuracy was 97.32%(109/112). Conclusion: Multi-slice spiral CT phase III enhanced scanning has important clinical value in differentiating small cell lung cancer from non-small cell lung cancer, and is worthy of further promotion and use in clinical practice.