Herein, we reported that hepatocellular carcinoma (HCC)‐derived VAMP‐associated protein A (VAPA)‐enriched LOs significantly promoted HCC bone‐specific metastasis by facilitating an osteoclastic PMN formation through neural Wiskott–Aldrich syndrome protein (N‐WASP)/actin related protein 2 (ARP2)/ARP3 signaling‐mediated fusion and activation of osteoclasts. The gene discussed is ACTR2; the disease is hepatocellular carcinoma.