Hepatocellular　carcinoma　(HCC)　is　a　common　malignancy　with　poor　prognosis.　In　recent　years,　immune　checkpoint　inhibitors　(ICIs)　have　enabled　breakthroughs　in　the　clinical　treatment　of　patients　with　HCC,　but　the　overall　response　rate　to　ICIs　in　HCC　patients　is　still　low,　and　no　validated　biomarker　is　available　to　guide　clinical　decision　making.　Here,　we　demonstrated　that　the　long　non-coding　RNA　Lnc-CCNH-8　is　highly　expressed　in　HCC　and　correlates　with　poor　prognosis.　Functionally,　elevated　Lnc-CCNH-8　inactivated　co-cultured　T　cells　in　vitro　and　compromised　antitumor　immunity　in　an　immunocompetent　mouse　model.　Mechanistically,　up-regulated　LncCCNH-8　can　sponge　microRNA　(miR)-217　to　regulate　the　expression　of　PD-L1.　In　addition,　Lnc-CCNH-8　can　also　stabilize　PD-L1　through　miR-3173/PKP3　axis.　Furthermore,　mice　bearing　tumors　with　high　Lnc-CCNH-8　expression　had　significant　therapeutic　sensitivity　to　anti-PD-L1　monoclonal　antibody　treatment.　More　important,　HCC　patients　with　high　levels　of　plasma　exosomal　Lnc-CCNH-8　had　a　better　therapeutic　response　to　ICIs.　Taken　together,　our　results　reveal　the　function　of　Lnc-CCNH-8　in　inducing　immune　escape　from　CD8+　T-cell-mediated　killing　by　up-regulating　PD-L1　in　a　miR-217/　miR-3173-dependent　manner,　which　also　reveals　a　novel　mechanism　of　PD-L1　regulation　in　HCC,　and　exosomal　Lnc-CCNH8　can　serve　as　a　predictive　marker　for　immunotherapy　response　in　HCC.