Background: Hepatorenal syndrome (HRS) is a life-threatening complication of advanced liver disease, characterized by functional renal failure and poor prognosis. Evidence on its burden and associated factors in Ghana remains scarce. Methods: A hospital-based cross-sectional study was conducted between February and May 2025 among 80 adult patients with liver disease. Sociodemographic and clinical data were obtained using structured questionnaires. Venous blood samples were analyzed for liver and renal function parameters using a fully automated chemistry analyzer. Data were analyzed with SPSS version 26.0. Associations were evaluated using Spearman’s correlation and binary logistic regression, with statistical significance set at p < 0.05. Results: Liver disease was diagnosed in 68.8% of participants, among whom 58.2% had hepatorenal syndrome. The prevalence of HRS was higher in females (68.0%) than males (50.0%), though this difference was not statistically significant (p = 0.178). Renal dysfunction was widespread: 93.8% of participants had reduced estimated glomerular filtration rate, and 98.8% had elevated blood urea nitrogen levels. Alkaline phosphatase was elevated in all participants, while gamma-glutamyl transferase was elevated in 80%. Logistic regression showed increased odds of HRS among patients not on medication (OR = 3.49) and those with prior hospitalization (OR = 2.30), although these associations did not reach statistical significance. Conclusion: Hepatorenal syndrome is highly prevalent among liver-diseased patients at Medylife Healthcare Hospital, indicating a substantial burden of renal dysfunction. Early renal monitoring, medication adherence, and integrated multidisciplinary care are essential to reduce morbidity and improve outcomes in this population.