In recent years, novel findings have progressively and promisingly supported the potential role of Artificial intelligence (AI) in transforming the management of various neoplasms, including hepatocellular carcinoma (HCC). HCC represents the most common primary liver cancer. Alarmingly, the HCC incidence is dramatically increasing worldwide due to the simultaneous "pandemic" spreading of metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD currently constitutes the leading cause of chronic hepatic damage (steatosis and steatohepatitis), fibrosis, and liver cirrhosis, configuring a scenario where an HCC onset has been reported even in the early disease stage. On the other hand, HCC represents a serious plague, significantly burdening the outcomes of chronic hepatitis B (HBV) and hepatitis C (HCV) virus-infected patients. Despite the recent progress in the management of this cancer, the overall prognosis for advanced-stage HCC patients continues to be poor, suggesting the absolute need to develop personalized healthcare strategies further. In this "cold war", machine learning techniques and neural networks are emerging as weapons, able to identify the patterns and biomarkers that would have normally escaped human observation. Using advanced algorithms, AI can analyze large volumes of clinical data and medical images (including routinely obtained ultrasound data) with an elevated accuracy, facilitating early diagnosis, improving the performance of predictive models, and supporting the multidisciplinary (oncologist, gastroenterologist, surgeon, radiologist) team in opting for the best "tailored" individual treatment. Additionally, AI can significantly contribute to enhancing the effectiveness of metabolomics-radiomics-based models, promoting the identification of specific HCC-pathogenetic molecules as new targets for realizing novel therapeutic regimens. In the era of precision medicine, integrating AI into routine clinical practice appears as a promising frontier, opening new avenues for liver cancer research and treatment.