The present disclosure provides a new series of 8-hydroxyquinoline derivatives/analogs that are potent KDM4 inhibitors with high activity and selectivity against KDM4 enzymes. Also disclosed are the pharmaceutical compositions comprising such 8-hydroxyquinoline-based potent KDM4 inhibitors, or a pharmaceutically acceptable salt thereof, and method of use thereof, for treating cancer and neoplastic diseases and the like.