Cancer remains one of the leading causes of morbidity and mortality worldwide, with hepatocellular carcinoma (HCC) accounting for ~75% of all primary liver cancers and exhibiting a high incidence rate. Unfortunately, the response rate to chemotherapeutic agents for liver cancer is relatively low, primarily due to the development of drug resistance and the lack of targeted therapeutic agents. The present study focused on the anticancer mechanisms of quercetin and the development of innovative nanocarriers designed to enhance its efficacy against HCC while mitigating drug resistance. Quercetin demonstrates a diverse array of biological activities, making it a promising candidate for therapeutic applications. Its mechanisms include inhibition of tumor cell cycle, induction of apoptosis, modulation of reactive oxygen species and inhibition of chemotherapeutic resistance. Given these properties, extensive research has been conducted in pharmaceutical engineering to develop well-designed nanocarriers that incorporate quercetin. These nanocarriers aim to improve the bioavailability and targeting of quercetin, thereby enhancing its therapeutic efficacy against HCC and overcoming the challenges associated with anticancer drug resistance. Through this approach, quercetin could potentially play a pivotal role in the future of HCC treatment, providing a synergistic effect when combined with traditional chemotherapy leading to improved patient outcomes.