Naturally occurring compounds are considered promising for testing in cancer therapy due to their expected multifaceted actions and low toxicity. These compounds are seen as potential anti-cancer agents in both standard and combination therapy. In this review, it is unveiled that quercetin can directly interact with DNA and initiate apoptosis in cancer cell lines and tumor tissues through the activation of different pathways. It was shown that quercetin exhibits synergism with anticancer drugs, making it an ideal flavonoid for consumption during cancer therapy. To address challenges such as slow response with small molecules, low solubility, and low bioavailability, various strategies are stated. Besides its anticancer properties, quercetin exhibits geno-protective, anti-inflammatory, and wound-healing activities. Quercetin has demonstrated satisfactory antitumor effectiveness by inducing apoptosis, halting the cell cycle, reducing metastasis and angiogenesis, reversing drug/radiotherapy resistance, and modulating tumor immunity.In this article, an overview of the anticancer properties of quercetin targeting different hallmarks of cancer and its synergistic activity with other natural compounds or chemotherapeutic agents to inhibit carcinogenesis by modulating various cellular pathways involved in cancer development was provided to enhance therapeutic efficacy in cancer treatment.