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Hepatocellular carcinoma (HCC) is the fourth major contributor to cancer-related deaths worldwide, and patients mostly have poor prognosis. Although several drugs have been approved for the treatment of HCC, cisplatin (CDDP) is still applied in treatment of HCC as a classical chemotherapeutic drug. Unfortunately, the emergence of CDDP resistance has caused HCC patients to exhibit poor drug response. How to mitigate or even reverse CDDP resistance is an urgent clinical issue to be solved. Because of critical roles in biological functional processes and disease developments, non-coding RNAs (ncRNAs) have been extensively studied in HCC in recent years. Importantly, ncRNAs have also been demonstrated to be involved in the development of HCC to CDDP resistance process. Therefore, this review highlighted the regulatory roles of ncRNAs in CDDP resistance of HCC, elucidated the multiple potential mechanisms by which HCC develops CDDP resistance, and attempted to propose multiple drug delivery systems to alleviate CDDP resistance. Recently, ncRNA-based therapy may be a feasible strategy to alleviate CDDP resistance in HCC. Meanwhile, nanoparticles can overcome the deficiencies in ncRNA-based therapy and make it possible to reverse tumor drug resistance. The combined use of these strategies provides clues for reversing CDDP resistance and overcoming the poor prognosis of HCC., (Copyright © 2022. Published by Elsevier Ltd.)