Abstract: Chondrosarcoma is the second most common malignant bone tumor with a potent capacity to invade locally and cause distant metastasis and accounts for approximately 20% of malignant bone lesions. Various tumor suppressor genes, oncogenes, cytokines, and intricate networks of signaling cascades have been associated with chondrosarcoma. The malignant cartilage-producing is associate with the loss of chromosomes or karyotypic alterations. The abnormal expression of CCN6, WISP-1, HMGB-1, TNF-α, IL-6, IGF and COXs have increased the migration of human chondrosarcoma cells by activating a series of signal transduction pathways and molecules. In recent years, accumulating studies have suggested their association with the pathogenesis of chondrosarcoma. This article reviews the role of these factors in the genesis and development of human chondrosarcoma.