Programmed cell death 1 (PD-1) inhibitor revives the killing effect of immune cells to prevent tumor progression. The present study aimed to evaluate the efficacy and safety of first-line PD-1 inhibitor + chemotherapy vs. standard treatment in recurrent or metastatic (R/M) oral squamous cell carcinoma (OSCC). A total of 51 patients with R/M OSCC were reviewed and divided into the PD-1 inhibitor + chemotherapy (n=21) and standard treatment (n=30) groups based on their actual treatments. The results of the present study demonstrated that the objective response rate (52.4 vs. 36.7%, P=0.265) and disease control rate (81.0 vs. 70.0%, P=0.377) were numerically elevated in the PD-1 inhibitor + chemotherapy group compared with those in the standard treatment group; however, the results did not reach statistical significance. The progression-free survival (PFS) was numerically increased (without statistical significance) in the PD-1 inhibitor + chemotherapy group compared with that of the standard treatment group (P=0.057). Specifically, the PD-1 inhibitor + chemotherapy group and the standard treatment group exhibited a median [95% confidence interval (CI)] PFS duration of 6.7 (1.6-11.8) and 5.2 (3.4-7.0) months, respectively. In addition, the PD-1 inhibitor + chemotherapy group demonstrated increased overall survival (OS) compared with that of the standard treatment group (P=0.032). Specifically, the PD-1 inhibitor + chemotherapy group and the standard treatment group exhibited a median (95% CI) OS duration of 18.3 (11.9-24.7) and 10.3 (7.9-12.7) months, respectively. Furthermore, multivariate Cox regression analysis indicated that PD-1 inhibitor + chemotherapy was independently associated with improved PFS [hazard ratio (HR)=0.308, P=0.002] and OS (HR=0.252, P=0.003). In addition, the incidence of grade 3-5 adverse events (AEs) was relatively low in both groups and the incidence of any grade of each AE was not significantly different between groups (all P>0.050). In conclusion, the first-line PD-1 inhibitor + chemotherapy group had improved efficacy and comparable safety compared with those of the standard treatment in patients with R/M OSCC.