Hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) presents a significant challenge, with recurrence rates ranging from 8% to 20% globally. Current biomarkers, such as alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), lack specificity, limiting their utility in risk stratification. YKL-40, a glycoprotein involved in extracellular matrix remodeling, hepatic stellate cell activation, and immune modulation, has emerged as a promising biomarker for post-LT surveillance. Elevated serum levels of YKL-40 are associated with advanced liver disease, tumor progression, and poorer post-LT outcomes, highlighting its potential to address gaps in early detection and personalized management of HCC recurrence. This manuscript synthesizes clinical and mechanistic evidence to evaluate YKL-40's predictive utility in post-LT care. While preliminary findings demonstrate its specificity for liver-related pathologies, challenges remain, including assay standardization, lack of prospective validation, and the need to distinguish between malignant and non-malignant causes of elevated levels. Integrating YKL-40 into multi-biomarker panels with AFP and DCP could enhance predictive accuracy and enable tailored therapeutic strategies. Future research should focus on multicenter studies to validate YKL-40's clinical utility, address confounding factors like graft rejection and systemic inflammation, and explore its role in predictive models driven by emerging technologies such as artificial intelligence. YKL-40 holds transformative potential in reshaping post-LT care through precision medicine, providing a pathway for better outcomes and improved management of high-risk LT recipients.