Background <p>Family relationships play a crucial role in the care and support of patients with terminal cancer, impacting their physical and emotional well-being. This study investigates whether family relationships are associated with caregiver responses in end-of-life (EOL) care for patients with terminal cancer.</p> Methods <p>This cross-sectional study analyzed data from 172 family caregivers of patients with terminal cancer, collected from nine hospice and palliative care centers in South Korea between June 2021 and May 2023. Standardized tools, including the Caregiver Reaction Assessment (CRA) and the Korean Family Relationship Assessment Scale (FRAS), assessed caregiver burden and family relationships. Analyses were adjusted for variables such as age, gender, marital status, employment status, presence of a spouse, religion, caregiving environment, social support, psychological resilience, and emotional distress. Multivariate regression and subgroup analyses were performed to examine these associations.</p> Results <p>The overall FRAS score was significantly correlated with all five domains of caregiver burden, adjusting for various factors (<i>p</i> &lt; 0.01). The financial problems domain of the CRA was positively correlated with family conflict (<i>p</i> &lt; 0.01); however, no correlation was observed with family support and togetherness. In the self-esteem domain of the CRA, positive correlations were observed among caregivers who were older adults, females, spouses, those with lower education levels, married, and those experiencing high emotional distress (<i>p</i> &lt; 0.01). Subgroup analyses revealed variations based on age, gender, caregiver relationship, social support level, resilience, and emotional distress.</p> Conclusions <p>These findings emphasize the integral role of family relationships in shaping caregiver experiences for patients with terminal cancer during EOL care.</p>