Abstract—Liver cancer has been plaguing the world with its high incidence and mortality rates. Existing targeted therapy, immunotherapy, and chemotherapy have shortcomings such as drug resistance, obvious adverse reactions, and limited efficacy, so there is an urgent need to develop new treatment strategies. Natural Bioactive Constituents (NCBs) have become a research hotspot in liver cancer due to their multi-target, multi-pathway, and low-toxicity characteristics. This article searched relevant databases and systematically reviewed the anti-liver cancer mechanisms of active ingredients in natural medicines, including cell cycle regulation, induction of apoptosis, and ferroptosis. At the same time, it explored the application value of the combined strategy of NCBs. It also summarizes the innovative applications of passive, active, and physicochemically targeted delivery systems in overcoming the physicochemical drawbacks of natural drugs and enhancing their bioavailability.