Abstract: Objective To analyze the incidence and severity grading of treatment-related adverse event (TRAE) associated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with various anticancer regimens. Methods A total of 356 tumor patients treated with PD-1/PD-L1 inhibitors were retrospectively selected as the study objects. The occurrence of adverse reactions in patients treated with PD-1/PD-L1 inhibitors combined with different anticancer regimens was recorded and analyzed. Results Among the 356 patients treated with PD-1/PD-L1 inhibitors in combination with various anticancer regimens, 332 times of TRAEs were observed. Fatigue and adverse gastrointestinal reactions were the most prevalent, accounting for 31.93% (106/332) and 20.78% (69/332) respectively. Skin-related adverse reactions (appearing within 3 to12 weeks) and gastrointestinal adverse reactions (5 to 10 weeks) occurred first, while fever (10 to 30 weeks) and pneumonia (12 to 32 weeks) presented later, with the longest observation time span. The lowest overall incidence of TRAE was observed in the combination of PD-1/PD-L1 inhibitors with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors (85.71%, 36/42), while the highest was in the combination with platinum-based doublet chemotherapy (96.88%, 155/160). The incidence of grade 3 to 5 TRAEwas lowest in the combination of PD-1/PD-L1 inhibitors with radiotherapy (10.53%, 6/57) and highest in the combination with vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) targeted therapy (44.64%, 25/56). There was no significant difference in the incidence and severity of TRAE among different tumors (P>0.05). Conclusion When different anti-cancer regiments combined with PD-1/PD-L1 inhibitors, the overall incidence of TRAE is higher, among which the incidence of TRAE combined with CTLA-4 is relatively lowest, and the symptoms of TRAE combined with radiotherapy are relatively mild.