Objectives <p>To characterize the clinicopathologic features of patients with oral squamous cell carcinoma (OSCC) and evaluate the prognostic significance of the history of oral potentially malignant disorders (OPMDs) in this population.</p> Materials and methods <p>This retrospective, single-center study enrolled 1140 patients from 2000 to 2017 to explore the clinicopathologic features of OSCC patients. After 2:1 propensity score matching, 129 patients with OPMD history (OPMD group) and 258 patients without OPMD history (non-OPMD group) were analyzed in a cohort study. The primary endpoint was overall survival (OS), while the secondary endpoint included disease-specific survival (DSS).</p> Results <p>Among the 1140 OSCC patients, only 17.0% had a well-documented history of OPMDs. The most common tumor site was the tongue (57.3%), and the majority of patients (85.7%) were over 40 years old. Compared to the non-OPMD group, the OPMD group exhibited significantly lower T and N stages, better differentiation, less frequent neck dissection, and shorter hospital stays. However, there were no significant differences in 5-year OS or DSS between the two groups.</p> Conclusion <p>Most OSCC patients lacked a defined history of OPMDs, which may reflect rapid malignant progression of oral lesions. These findings underscore the importance of enhanced vigilance and early diagnostic interventions for OPMDs and OSCC, particularly in individuals over 40 years of age.</p> Clinical trial number <p>ChiCTR2200065588, Registration Date: 09 Nov. 2022.</p>