Introduction: Caring for patients receiving hemodialysis places a burden on caregivers. Objectives: To examine caregiving burden and depression in the family caregivers of patients receiving hemodialysis and associated factors. Methods: A cross-sectional design was used. Participants were 204 adult caregivers of patients receiving hemodialysis. Questionnaires included sociodemographic characteristics, the Oberst Caregiving Burden Scale-Difficulty (OCBS-D) subscale, Bakas Caregiving Outcomes Scale (BCOS), and the Patient Health Questionnaire-9 to measure the burden and depression of caregivers. Descriptive statistics, two linear regression analyses, and multinomial logistic regression were used in data analysis. Results: The majority (59.0%, n = 120) of caregivers had a moderate level of depression with scores ranging from 11 to 16. The analysis showed that the mean score of OCBS-D was 42.0 (SD = 4.7) with scores ranging from 26.9 to 58.9 (range = 32.0), while the caregivers' mean score of BCOS was 52.1 (SD = 9.3) with scores ranging from 38.0 to 82.5 (range = 44.5). Given that the expected score of OCBS-D and BCOS ranged from 15 to 75 and 15 to 105, respectively, the analysis indicated a moderate to a high level of burden among caregivers. Age and travel time were associated with a higher likelihood of negative outcomes in the family caregivers, while higher patient age was associated with a greater caregiver burden. Relevance to Clinical Practice: It is important to assess and address the practical issues that caregivers experience, such as employment-related responsibilities, financial difficulties, and the need to learn specific skills related to patients’ chronic illnesses. Conclusion: Caregivers of patients receiving hemodialysis are likely to experience moderate depression and burden. Caregiver burden increases with patient age and travel time to the hemodialysis units.