Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck. Programmed cell death protein 1 (PD-1), and programmed cell death 1 ligand 1 (PD-L1) are often overexpressed in OSCC patients, and their expression level is closely related to tumor prognosis. The objectives of this study were: 1) to evaluate the impact of anti-PD-1 treatment on the immune system and prognosis of OSCC patients and 2) to find possible associations between T-cell immunity and anti-PD-1 therapy.Methods: A total of 120 patients (divided into two equal groups: "non-anti-PD1 therapy " and "anti-PD1 therapy ") with pathologically diagnosed OSCC participated in the study. Fresh peripheral blood samples (1 mL) were collected 2 days before and 20 days after the treatment. Heparin was used as an anticoagulant. Kaplan-Meier curves were plotted to compare the non-anti-PD-1 therapy and anti-PD-1 therapy groups.Results: Based on the Spearman-rho test, we found a significant correlation between anti-PD-1 treatment and survival time (P < 0.001). Univariate/multivariate Cox regression analysis revealed that anti-PD-1 therapy is a significant independent risk factor of 5-year overall survival (OS) in OSCC patients (HR: 0.110, 95% CI: 0.062-0.195, P < 0.001). One-way ANOVA showed that the mean levels of IFN-gamma and IL-2 and numbers of CD4+ T cells were significantly increased in the anti-PD-1 therapy group compared with the non-anti PD-1 therapy group (control). The was no change in the number of CD8+ cells between the two groups. Kaplan-Meier curve results showed that the OS of patients in the anti-PD-1 therapy group was significantly longer than that in the non-anti-PD-1 therapy group.Conclusion: Anti-PD-1 therapy is beneficial to the survival and prognosis of patients with OSCC, improves T-cell immunity, and enhances tumor regression.