肝细胞癌（HCC）目前是常见的癌症死因之一，近年来患者生存率并未有明显改变。尽管传统的HCC患者治疗主要包括手术、化疗和放疗，取得了令人钦佩的成就，但仍存在挑战，如药物耐药性和毒性。以聚集的正规间隔短回文重复序列/CRISPR相关核酸酶9（CRISPR/Cas9）为基础的新型基因治疗，作为传统治疗方法的替代品，已引起了广泛关注，用于根除耐药恶性肿瘤和调控目标基因编辑的多个关键事件。最近，CRISPR/Cas9-based抗药物在化学、材料科学、肿瘤生物学和遗传学交叉领域取得了进展。本综述首先介绍了CRISPR/Cas9技术的原理和状态，以展示其可行性。此外，重点介绍了CRISPR/Cas9技术在治疗HCC中的应用。进一步，概述了非病毒载体系统在HCC治疗中CRISPR/Cas9-based抗药物的设计、作用机制和抗癌应用。最后，讨论了当前研究的局限性和前景，并希望为抗药物设计提供全面的理论基础。© 2023 Elsevier B.V. 代表沈阳药科大学出版

Hepatocellular carcinoma (HCC) is now a common cause of cancer death, with no obvious change in patient survival over the past few years. Although the traditional therapeutic modalities for HCC patients mainly involved in surgery, chemotherapy, and radiotherapy, which have achieved admirable achievements, challenges are still existed, such as drug resistance and toxicity. The emerging gene therapy of clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9-based (CRISPR/Cas9), as an alternative to traditional treatment methods, has attracted considerable attention for eradicating resistant malignant tumors and regulating multiple crucial events of target gene-editing. Recently, advances in CRISPR/Cas9-based anti-drugs are presented at the intersection of science, such as chemistry, materials science, tumor biology, and genetics. In this review, the principle as well as statues of CRISPR/Cas9 technique were introduced first to show its feasibility. Additionally, the emphasis was placed on the applications of CRISPR/Cas9 technology in therapeutic HCC. Further, a broad overview of non-viral delivery systems for the CRISPR/Cas9-based anti-drugs in HCC treatment was summarized to delineate their design, action mechanisms, and anticancer applications. Finally, the limitations and prospects of current studies were also discussed, and we hope to provide comprehensively theoretical basis for the designing of anti-drugs.© 2023 Published by Elsevier B.V. on behalf of Shenyang Pharmaceutical University.