BACKGROUND: Immunotherapy using PD-1 or PD-L1 inhibitors has been increasingly reported in a variety of non-melanoma skin cancers (NMSCs). OBJECTIVE: To analyze the evidence of PD-1 and PD-L1 inhibitors in the treatment of non-melanoma skin cancer. METHODS: A primary literature search was conducted with PubMed, Cochrane Library EMBASE, Web of Science, and CINAHL through October 28, 2018 to include studies on the use of PD-1 or PD-L1 inhibitor in human subjects for non-melanoma skin cancer. Two reviewers independently performed study selection, data extraction and critical appraisal. RESULTS: Fifty-one articles were included in this systematic review. The most robust evidence was in the treatment of Merkel cell carcinoma and cutaneous squamous cell carcinomas, as supported by phase 1 and 2 clinical trials. Treatment of basal cell carcinoma, cutaneous sarcoma, sebaceous carcinoma and malignant peripheral nerve sheath tumor also showed benefit with PD-1/PD-L1 inhibitors but data is limited. There does not appear to be efficacy for PD-1/PD-L1 inhibitors in cutaneous lymphomas. LIMITATIONS: More investigation is needed to determine the efficacy, tumor responsiveness, and the safety profile of PD-1 and PD-L1 inhibitors in NMSC. CONCLUSION: PD-1 and PD-L1 inhibitors exhibit treatment efficacy in a variety of non-melanoma skin cancers.