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Background Being involved in caring for family members during illness is part of the Indonesian culture, even during hospitalization. It is unknown which factors influence the quality of life (QoL) of family members taking care of their loved ones. The present study aims to identify factors influencing the QoL of family caregivers of hospitalized patients with cancer in Indonesia. Methods A cross-sectional survey was performed. Data were collected in a general hospital in Yogyakarta from September to December 2011. Family caregivers of patients with cancer were invited to participate. Regression analysis was used to determine which aspects of caring and which demographic characteristics influenced their QoL. The Caregiver QoL Index-Cancer questionnaire was used to measure the QoL. Results One hundred of 120 invited caregivers (83%) completed the questionnaire. Being involved in psychological issues in caring ( β = 0.374; p = 0.000), younger age ( β = −0.282; p = 0.003), no previous caring experience ( β = −0.301; p = 0.001), and not being the spouse ( β = −0.228; p = 0.015) negatively influenced the QoL and explained 31% of the variation (adjusted R2 = 0.312; F = 12.24; p = 0.000). Gender, education level, and time spent on caring did not influence the QoL of family caregivers. Conclusions Our findings identified modifiable factors such as dealing with psychological issues and lack of experience in caring that negatively influenced the QoL of family caregivers. These factors are potential targets for intervention strategies. Education and intervention programs focusing on dealing with psychological problems in cancer care might improve the QoL of both patients and their families. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]