Objective To synthesize and investigate cytotoxicity of an indole-chalcone derivative FC58. Methods The target compound was synthesized through the Aldol condensation with 1-(3,4,5-trimethoxyphenyl)ethan-1-one and 1H-indole-3-carbaldehyde. The Cell Titer-Blue method was used to determine in vitro cytotoxicity. The cell cycle experiment was performed to analyze the action characteristics of FC58. Results FC58 exhibited high cytotoxicity against various leukemia cells and resulted in G2/M phase arrest. It showed stronger drug resistant index than traditional tubulin inhibitors such as paclitaxel, vinblastine and doxorubicin. Conclusion FC58 represents a promising lead compound for multi-drug resistant leukemia.