Hepatocellular Carcinoma (HCC) is one of the most common types of primary liver cancer. Current treatment options have limited efficacy against this malignancy, primarily owing to difficulties in early detection and the inherent resistance to existing drugs. Tumor heterogeneity is a pivotal factor contributing significantly to treatment resistance and recurrent manifestations of HCC. Intratumoral heterogeneity is an important aspect of the spectrum of complex tumor heterogeneity and contributes to late diagnosis and treatment failure. Therefore, it is crucial to thoroughly understand the molecular mechanisms of how tumor heterogeneity develops. This review aims to summarize the possible molecular dimensions of tumor heterogeneity with an emphasis on intratumoral heterogeneity, evaluate its profound impact on the diagnosis and therapeutic strategies for HCC, and explore the suitability of appropriate pre-clinical models that can be used to best study tumor heterogeneity; thus, opening new avenues for cancer treatment.

肝细胞癌（HCC）是最常见的原发性肝癌类型之一。目前的治疗方案对这种恶性肿瘤的疗效有限，主要是由于早期检测的困难以及对现有药物固有的耐药性。肿瘤异质性是导致 HCC 治疗耐药和复发的关键因素。肿瘤内异质性是复杂肿瘤异质性谱系的一个重要方面，并导致晚期诊断和治疗失败。因此，深入了解肿瘤异质性发生的分子机制至关重要。本综述旨在总结肿瘤异质性可能的分子维度，重点关注瘤内异质性，评估其对 HCC 诊断和治疗策略的深远影响，并探索可用于最佳研究肿瘤的适当临床前模型的适用性异质性；因此，开辟了癌症治疗的新途径。