CONTEXT: A better time-to-death (TTD) prediction can facilitate decision-making processes related to plans for providing effective end-of-life care for patients in hospice wards. OBJECTIVE: To explore the association of cardiovascular autonomic functions with TTD in patients with terminal hepatocellular carcinoma. METHODS: A prospective study was conducted with 33 patients with hepatocellular carcinoma recruited from the hospice ward of a regional hospital in Chiayi county, Taiwan. Serum creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, blood urea nitrogen (BUN), and serum albumin were measured on the admission day. Cardiovascular autonomic functions were evaluated by frequency-domain measures of heart rate variability (HRV) on admission. RESULTS: TTD was significantly associated with total spectrum power (TP) (r=0.55, P=0.001) and high frequency (HF power) (r=0.44, P=0.010) of HRV measurement. The accuracy of within-one-week TTD prediction was 67% for TP and HF power. The accuracy of within-two-week TTD prediction was 82% for TP and 73% for HF. In addition, TTD of the patients was also significantly associated with serum creatinine (r=-0.42, P=0.015), serum albumin (r=-0.46, P=0.007), and BUN (r=-0.44, P=0.010). CONCLUSION: This is the first study to evaluate the association between cardiovascular autonomic functions and TTD in patients with terminal hepatocellular carcinoma. The inclusion of HRV measurement in prognostic models may improve accuracy in TTD prediction and, hence, facilitate medical decision making in hospice care.