AUTHOR=Ramalingam Prasanna Srinivasan , Zhang Liming , Hussain Md Sadique , Khan Gyas , Mawkili Wedad , Hanbashi Ali , Gupta Gaurav , Balakrishnan Purushothaman , Arumugam Sivakumar TITLE=Non-coding RNAs as key regulators in hepatitis B virus-related hepatocellular carcinoma JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1602252 DOI=10.3389/fimmu.2025.1602252 ISSN=1664-3224 ABSTRACT=Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a significant global health challenge due to its high prevalence and poor prognosis. Recent advances have revealed that non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs, circular RNAs, and small nucleolar RNAs, play critical regulatory roles in HBV-induced oncogenesis. These ncRNAs modulate various cancer hallmarks and contribute to HCC progression. Notably, their stability, detectability in bodily fluids, and disease-specific expression patterns render these ncRNAs as highly promising diagnostic and prognostic biomarkers for HBV-HCC. Herein, we review the types and mechanisms of HBV-related ncRNAs, emphasizing their dual roles as oncogenes and tumor suppressors. Furthermore, we discuss their applicability as diagnostic markers and therapeutic targets and review recent directions in ncRNA-based approaches that aim to enhance patient treatment. Concerning these aspects, the present review aimed to provide an understanding of the complexity of ncRNAs in HBV-related HCC with the hope of directing future research and developments towards effective control of this complex malignancy known as HCC.