Family caregivers endure the burden of caring for patients receiving hemodialysis, which can affect their psychological status and may disrupt the care process. This study aims to assess the level of burden, anxiety, depression, and quality of life (QOL) among family caregivers, to investigate the influence of caregivers’ sociodemographic factors and patients’ clinical conditions on the level of burden, and investigate how burden affects anxiety/depression and QOL. A descriptive, cross-sectional study was conducted from September to October 2020. A total of 104 caregivers with a mean age of 44.4 ± 12.7 years (63.5% women) in the hemodialysis department of a hospital in Indonesia were examined. Zarit Burden Interview (ZBI), Hospital Anxiety and Depression Scale, and WHOQOL-BREF were used. Descriptive analysis was conducted to assess the level of psychological status, and multiple regression analysis and path analysis were performed to evaluate the association among all factors. As result, regarding burden, 10.2% had a moderate-to-severe burden, and in terms of anxiety and depression, 25% and 9.6% showed abnormal cases; the mean scores of 4 domains of QOL were about 60 points. Burden and anxiety/depression were significantly negatively associated with all domains of QOL (p < 0.001); however, sociodemographic and clinical factors were not associated with any of the QOL domains. The path analysis results showed that burden positively correlated with anxiety/depression and negatively correlated with QOL via anxiety/depression. In conclusion, family caregivers’ QOL was found to be indirectly influenced by burden through anxiety/depression. Further evaluation of clinical significance and implications for caregiver’s lifestyle regarding anxiety and depression, which result in caregiver burden, is warranted.