Background: There is limited experience of PD-1 combined with other therapies in children. We aimed to explore the antitumor activity and safety of PD-1 antibody monotherapy or combination with other regimens in relapsed or refractory pediatric cancer. Methods: This was an observational retrospective study performed at two academic medical centers (Sun Yat-sen University Cancer Center and Nanfang Hospital, Southern Medical University) The primary objective of this study was to describe the overall response rate (ORR) and disease control rate (DCR). Secondary objectives included characterizing toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as well as describing progression free survival (PFS) and overall survival (OS). Results: Of the 22 pediatric cancer patients who received PD-1 inhibitors, the median follow-up for all patients after the commencement of PD-1 therapy with or without other regimens was 12.3 months (0-43 months). The objective response rate (ORR) and disease control rate (DCR) of the 6 patients with HL were 83.3% (3CR and 2PR) and 100%, respectively. No objective response was observed in patients with melanoma or Burkitt lymphoma evaluated in this study. For patients treated with PD-1 inhibitor combination therapy, PD-1 antibody combined with decitabine showed potential efficacy in advanced pediatric cancer patients. One of the Three of patients who received PD-1 combined with decitabine achieved CR and another two other patients achieved PR. At the data cutoff, 10 of the 13 (76.9%) patients achieved disease control as the best objective response. The median PFS and OS were 90 days (95%CI: 10.733-169.267) and 158 days (95%CI: 131.514-184.486) respectively. There were no severe treatment-related adverse events (TRAEs) directly attributed to PD-1 monotherapy. The severe TRAEs are due to chemotherapy in the combination regimen. Conclusions: PD-1 monotherapy demonstrated antitumor activity in a population of pediatric patients with HL. The regimen of PD-1 inhibitor combined with decitabine showed potential in treating with pediatric cancer patients.