Abstract: Objective: We explored the application value of multi-slice spiral CT (MSCT) in preoperative prediction of the degree of pathological differentiation of peripheral lung squamous cell carcinoma (PLSCC). Methods: A total of 76 lesions from 75 patients with PLSCC confirmed by pathology in our hospital from January 2020 to November 2023 were selected and divided into a well-to-moderately differentiated group (n=55) and a poorly differentiated group (n=21) according to their pathological differentiation grades. The MSCT features of the two groups were compared and analyzed, including tumor size, shape, location, cavity, calcification, and signs of lobulation, air bronchogram, spiculation, vacuole, vascular convergence, pleural indentation, bronchial crawling, and bronchial truncation. Results: Compared with the poorly differentiated PLSCC group, the well-to-moderately differentiated PLSCC group had larger lesions, more signs of air bronchogram, and fewer signs of lobulation. These differences between groups were statistically significant. Conclusions: Some MSCT detected PLSCC features correlate with its degree of pathological differentiation and can be used to predict the pathological differentiation degree of PLSCC preoperatively.