In our study, we demonstrated inhibition of CacyBP/Myd88 signaling markedly reduced the CX3CL1-mediated chemotaxis of monocytes and macrophages, and increased the infiltration of CD4+ and CD8+ T cells in the TME, which provides a novel idea for improving therapeutic efficacy of anti-PD-1 antibodies in HCC. Here, CACYBP is linked to hepatocellular carcinoma.