Lymphoepithelioma‐like carcinoma (LELC) is an uncommon subtype of primary liver cancer with predominant lymphocyte infiltration and a relatively favorable outcome. However, no standard treatment for advanced hepatic LELC has been established. Here, we give a first report of a 60‐year‐old man with advanced hepatic LELC who had a high expression of PD‐L1 in tumor cells and a high level of tumor‐infiltrating leukocytes (TILs) in the tumor microenvironment (TME). After receiving six cycles of multiple receptor tyrosine kinase inhibitor (rTKI) with lenvatinib plus PD‐1 inhibitor toripalimab treatment, the patient achieved persistent partial response (PR). Our report indicates that advanced hepatic LELC with high expression of PD‐L1 may benefit from the combination of rTKI and PD‐L1/PD‐1 blockade. Therefore, this potential strategy should be considered when treating those rare liver cancers.
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