Hepatocellular carcinoma (HC) ranks as the fifth most prevalent form of cancer among humans and is a significant contributor to cancer-related deaths. During the latest year, an interesting scientific fascination arose around gold nanoparticles (AUNPs) following the recovery of their remarkable properties. Some studies suggest that AUNPs can enhance drug targeting in cancer treatment and reduce its toxicity. The major purpose of this paper is to systematically review the effectiveness, safety, and prospective mechanism of gold nanoparticles in delivering drugs for liver cancer treatment. Comprehensive research was conducted using major scientific databases (i.e., PubMed, Web of Science, and Scopus) to identify studies focusing on AUNPs in drug delivery systems. We mainly focused on studies that specifically analyzed liver cancer. The current results of the systematic review show that the application of gold nanoparticles (AUNPs) in liver cancer drug delivery enhances drug targeting to liver tumors. This efficient factor improves the bioavailability and elevates the therapeutic index of chemotherapeutic agents in treatment. This systematic review highlights the significant potential of AUNPs to increase the delivery of drugs for liver cancer treatment effectively. The major findings indicate that AUNPs improve the targeting and bioavailability of chemotherapeutic agents, enhancing therapeutic outcomes such as tumor suppression and improved survival rates. While the results of this review are encouraging; however, further research is necessary to ensure the safety and efficacy of AUNPs in clinical settings. Human trials must address concerns regarding long-term toxicity and regulatory approval.

(1) Background: Hepatocellular carcinoma (HCC) is a major global health issue, ranking among the most frequently diagnosed cancers and one of the leading causes of cancer-related mortality. (2) Methods: To identify studies that focus on nanotechnology-mediated treatment and early diagnosis in hepatocellular carcinoma, our group conducted a thorough literature search across major scientific databases. (3) Results: In this narrative review, we demonstrated that nanotechnology—particularly the use of nanoparticles—holds significant potential for both the treatment and early detection of hepatocellular carcinoma. Nanoparticles act as carriers for the targeted delivery of drugs to cancer cells, greatly enhancing treatment efficacy while minimizing adverse effects on healthy tissues. Due to their physicochemical properties, these nanoparticles can also carry contrast agents, enabling precise identification of tumor cells and contributing to the early diagnosis of hepatocellular carcinoma. (4) Conclusions: While significant progress has been made, challenges such as toxicity, cost, and regulatory hurdles remain.