Objectives This study aimed to investigate the association between salivary matrix metalloproteinase‐1 (MMP‐1) and clinicopathological parameters of oral cavity squamous cell carcinoma (OSCC) and compare the prognostic efficacy of salivary MMP‐1 and other established circulating markers for OSCC. Methods Saliva specimens from 479 OSCC subjects were examined using an enzyme‐linked immunosorbent assay. The area under the curve (AUC) values of salivary MMP‐1 and other markers were calculated, and survival analyses were conducted using Kaplan–Meier and multivariate regression methods. Results Salivary MMP‐1 showed good discrimination in predicting overall survival, with an AUC of 0.638, which was significantly higher than that of albumin (0.530, p = .021) and Charlson comorbidity index (0.568, p = .048) and comparable with neutrophil‐to‐lymphocyte ratio (0.620, p = .987), platelet‐to‐lymphocyte ratio (0.575, p = .125), and squamous cell carcinoma antigen (0.609, p = .605). Elevated levels of salivary MMP‐1 were significantly associated with higher pT classification, pN classification, overall pathological stage, positive extranodal extension, tumor differentiation, positive lymphovascular invasion, positive perineural invasion, and tumor depth (p all <.05). Multivariate analyses indicated that a higher level of salivary MMP‐1 (≥2060.0 pg/mL) was an independent predictive factor of poorer overall survival (adjusted hazard ratio: 1.421 95% confidential interval: 1.014–1.989, p = .041). Conclusion The study found that the salivary MMP‐1 level was significantly associated with many adverse clinicopathological parameters of OSCC. In OSCC, it was found to have superior efficacy in predicting prognosis and was an independent prognostic factor of post‐treatment outcome. Level of evidence 3. Salivary MMP‐1 showed a significantly higher AUC than albumin and CCI and a higher or comparable AUC to the NLR, the PLR, and SCCA in predicting overall survival in OSCC patients. The study also indicates that patients with high levels of salivary MMP‐1 have poorer prognosis in terms of OS and DSS. Overall, these findings may facilitate development of a noninvasive and user‐friendly salivary detection tool for OSCC treatment.