<p>Primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), remains a leading cause of cancer-related death worldwide. Therapeutic resistance substantially limits the efficacy of chemotherapy, targeted therapy, immunotherapy, and radiotherapy. For example, only approximately 30% of patients with HCC derive clinical benefit from sorafenib, and acquired resistance commonly develops within six months, underscoring the urgent need to clarify the molecular basis of treatment failure. Circular RNAs (circRNAs) are covalently closed RNA molecules with high structural stability and tissue-specific expression. In liver cancer, circRNAs regulate therapeutic resistance through multiple mechanisms that converge on ferroptosis suppression, apoptosis evasion, DNA damage repair, oncogenic signaling, immune escape, and cancer stemness. Beyond the canonical competing endogenous RNA model, this review highlights emerging regulatory mechanisms involving RNA-binding protein interactions, circRNA-encoded functional micropeptides, and circRNA-mediated phase separation. Exosomal circRNAs also facilitate the intercellular transmission of resistant phenotypes and remodel the tumor immune microenvironment. We systematically summarize circRNA-mediated resistance across different therapeutic modalities and critically evaluate the available evidence according to experimental models, in vivo validation, and patient validation. Although circRNAs show potential as biomarkers for predicting therapeutic response and as targets for overcoming resistance, most candidates remain at the preclinical stage. Their clinical translation is constrained by the lack of standardized detection methods, insufficient multicenter validation, and inefficient and inadequately targeted in vivo delivery systems. Because most direct mechanistic evidence is derived from HCC, selected iCCA-related findings are incorporated where available.</p>