Abstract: OBJECTIVE To explore the risk factors related to serious adverse drug reactions(ADR) caused by pembrolizumab in the treatment of advanced cancer, and to provide references for clinically safe and effective use of pembrolizumab and prevention of ADR. METHODS Retrospectively analyzed the clinical case data of all patients who had used pembrolizumab from January 2018 to June 2020, and conducted multivariate unconditional Logistic regression analysis on the risk factors that might cause severe ADR of pembrolizumab. RESULTS The results of univariate analysis of 138 patients using pembrolizumab showed that the history of drug allergy, drug administration dose and PD-L1 expression level were statistically significant(P<0.05). The selected influencing factors were carried out unconditional Logistic regression, the result showed that the expression level of PD-L1 in patients had a significant impact on the occurrence of severe ADR of pembrolizumab(P<0.05). CONCLUSION The clinical application of pembrolizumab leads to a higher proportion of severe ADR, especially in patients with a single high dose and high PD-L1 expression. The occurrence of ADR after administration should be closely observed, and patients with severe ADR should be actively treated symptomatically.