Objective To report the clinical characteristics of severe hepatotoxicity due to PD-1 inhibitors and the safety of rechallenge after hepatotoxicity.Methods A retrospective survey of 641 cancer patients treated with PD-1 inhibitors was conducted.Results Totally 10 out of the 641 patients (1.56%) developed severe hepatotoxicity, with a median time to onset of 53 d (1~265 d) and a median time to regression of 25 d (3~56 d). The type of hepatotoxicity was predominantly hepatocellular injury type, and some presenting as a mixed type. Ten patients recovered after hepatotoxicity. Only five patients challenged the PD-1 inhibitors again. Three of them suffered from hepatotoxicity again. Two of the three patients suffered from severe hepatotoxicity, resulting in permanent withdrawal of PD-1 inhibitors, and they had a different type of hepatotoxicity from the previous one.Conclusion Severe hepatotoxicity caused by PD-1 inhibitors has a good prognosis but eventually leads to permanent discontinuation of PD-1 inhibitors in most patients. In addition, half of the patients underwent rechallenge with PD-1 inhibitors, and a significant proportion of them experienced a severe recurrence of hepatotoxicity.