STUDY OBJECTIVE: How perioperative heart rate variability (HRV) indices differ according to the anxiety or depressed mood of patients scheduled to undergo a major surgical procedure for cancer. DESIGN: Prospective observational study. SETTING: Operating room. PATIENTS: Forty-one male patients between 40 and 70 years of age with hepatocellular carcinoma were included in the final analysis. INTERVENTIONS: HRV was measured on the day before surgery (T1), impending anesthesia (T2), and after anesthetic induction (T3). Preoperative anxiety and depressed mood of all patients were evaluated using the State-Trait Anxiety Inventory and Self-Rating Depression Scale (SDS). MEASUREMENTS AND RESULTS: HRV was significantly different among T1, T2, and T3. At T2, high frequency (HF) (normalized units of HF [nuHF]) was decreased and low frequency (LF) (normalized units of LF) and LF/HF were increased compared with those at T1 and T3. In the subgroup analysis between high and low SDS groups, high SDS group showed significantly decreased nuHF (P = .035), increased nuLF (P = .039), and increased LF/HF (P = .020) compared to low SDS group at T1. However, these values at T2 and T3 were not different between 2 groups. In analysis within the groups, low SDS group showed significant differences in nuHF, nuLF, and LF/HF among T1, T2, and T3 (P < .05, respectively), but no changes in these values were observed in high SDS group among the 3 different time points. CONCLUSIONS: HRV decreased significantly immediately before anesthesia and recovered to baseline with anesthetic induction. Preoperative, more depressed patients showed increased sympathetic tone at baseline and blunted response to impending anesthesia on the HRV measurements.