Mitochondrial dynamics describes the continuous balance between fission and fusion, which when disrupted—often toward excessive fission or impaired fusion—leads to abnormalities in organelle number, morphology, and function, with fragmentation being the hallmark feature observed across multiple cancer types. The liver, as a metabolic hub rich in mitochondria, is particularly susceptible to these alterations, and accumulating evidence implicates mitochondrial dynamics imbalance in liver cancer initiation, progression, and therapeutic resistance. This review systematically consolidates the molecular underpinnings of this imbalance in liver cancer and its translational relevance to diagnosis, treatment, and prognosis. The core regulatory machinery is dissected, including fission mediators (DRP1, FIS1, MFF), fusion proteins (OPA1, MFN1, MFN2), and upstream modulators such as miR- 761, GNPAT, and HBV. The emerging utility of mitochondrial dynamics-related markers for early liver cancer detection, risk stratification, and outcome prediction is then evaluated, followed by an analysis of their mechanistic contributions to chemoresistance, targeted therapy failure, and immune evasion, alongside current intervention strategies. The crosstalk between mitochondrial dynamics and the tumor microenvironment—particularly through immune cell functional modulation and metastasis promotion—is also discussed. Key advances in the field are summarized, while persistent barriers to clinical translation are acknowledged. Future efforts should prioritize mechanistic deepening and rigorous clinical validation to facilitate precision medicine in liver cancer.