To investigate the change and relationship between serum high-mobility group box-1(HMGB1) and related inflammatory cytokines level in patients suffer with bone metastatic pain. Collection of the bone cancer pain patients who received analgesic therapy the department of pain in The First Affiliated Hospital of Jiaxing University from November 2016 to August 2016. Serum concentration of HMGB1, the Receptor of Advanced Glycation Endproducts (RAGE), monocyte chemotactic protein-1(MCP-1), tumor necrosis factor -α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10), interleukin-13 (IL-13), and transforming growth factor-β (TGF-β) levels were determined in 15 healthy individuals as healthy donor and 15 patients with bone metastatic pain by enzyme-linked immunosorbent (ELISA) . The healthy individuals and patients with bone metastatic pain were collected before treatment and on 7 d after the treatment. The serum concentration of HMGB1 and RAGE were significantly increased in tumorous group compared with healthy group[(8.8±2.3) vs (1.9±1.1) μg/L,(231±16) vs (46±20) ng/L); 7.10,12.44, both 0.05], then decreased after analgesic therapy [(4.77±1.36) μg/L, (129.80±29.32) ng/L, 7.10, 12.44, both 0.05]. The serum concentration of proinflammatory cytokines such as MCP-1, TNF-α, and IL-1β were significantly increased in tumorous group when compared with healthy group, and decreased after analgesic therapy (all 0.05). The expression of anti-inflammatory cytokines such as IL-10, IL-13, and TGF-β were significantly increased in tumorous group when compared with healthy group, and decreased after analgesic therapy (all 0.05).Compared with healthy group, the levels of MCP-1/IL-10, MCP-1/IL-13, MCP-1/TGF-β, TNF-α/IL-10, TNF-α/IL-13, TNF-α/TGF-β, IL-1β/IL-10, IL-1β/IL-13, IL-1β/TGF-β were significantly increased in tumorous group (all 0.05). HMGB1 may adjust the proinflammatory-anti-inflammatory system homeostasis to participate in the development of bone metastatic pain.