BACKGROUND/AIM: The aim of this study was to establish an objective evaluation method for pain due to bone metastasis, based on heart rate variability (HRV). PATIENTS AND METHODS: In this prospective study, patients who underwent radiotherapy for painful bone metastases were enrolled. Pain was assessed using a numerical rating scale (NRS), and anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). Autonomic and physical activities were evaluated by measuring HRV using a wearable device. NRS, HADS, and R-R interval (RRI) values were obtained upon starting, completing, and 3-5 weeks after radiotherapy. RESULTS: Between July 2020 and July 2021, 11 patients were enrolled. The median average NRS score was 5 (range=2-10). HADS-assessed median anxiety and depression scores were 8 (range=1-13 and 2-21). For patients with an NRS score >/=4, NRS score was significantly associated with low-frequency/high-frequency (LF/HF) component ratio (p=0.03). Heart rate during physical activity was significantly higher than resting heart rate; however, mean resting LF/HF was significantly higher than LF/HF during physical activity. During rest, excluding patients with a HADS depression score >/=7 in an NRS score 1-3, there was a trend for a positive correlation between the NRS score and the mean LF/HF (p=0.07). CONCLUSION: HRV measurements can objectively evaluate pain due to bone metastasis. However, we must consider that the effects of mental status, such as depression, on LF/HF also affect HRV in patients with cancer with mild pain.