MEG3 promotes M1 polarization and inhibits M2 polarization of BMDM by binding HuR, which suppresses CCL5 transcription. MEG3 overexpression inhibits HCC metastasis, invasion, and angiogenesis by blocking M2 polarization. MEG3 suppresses tumorigenesis by enhancing M1 and inhibiting M2 polarization, while CCL5 absence in M2 macrophages reverses MEG3’s inhibitory effects on migration, invasion, and lumen formation. This evidence concerns the gene MEG3 and hepatocellular carcinoma.