Abstract: OBJECTIVE The heterogeneous nature of cancer requires a comprehensive approach for attacking the multiple mechanisms underlying the initiation and progression of cancer. HDACi have emerged as a new class of anticancer agents, targeting the biological processes including cell cycle, apoptosis and differentiation. Design novel multi-target HDACi based on the structural diversity and adaptation. METHODS Classify and summarize large numbers of reported multi-target histone deacetylase inhibitors. RESULTS Multi-target inhibitors in clinical trials show good antitumor activity. CONCLUSION Multi-target single-molecule HDAC inhibitors have attracted much attention, and have broad prospects for development.