Objective: This study examined the quality of life (QOL) of caregivers for gastrointestinal (GI) cancer patients, and associated factors. Methods: A cross-sectional study was conducted at three referral hospitals in Klang Valley, Malaysia. A total of 323 pairs of patients and caregivers from the oncology units of these hospitals completed questionnaires in Malay. The QOL of caregivers was measured using The Malay Caregiver Quality of Life questionnaire. The independent variables were caregiver and patient factors, care-related factors, the Caregiver Strain Index-Malay, and the Multidimensional Scale of Perceived Social Support-Malay. Simple and multiple linear regression analyses were performed to determine the factors associated with the QOL. Variables with p < 0.05 were considered significant in the multiple analyses. Results: Female caregivers were 68.1% of the total, and 46.4% caregivers were spouses to cancer patients. Their mean age was 44.50 (13.29) years old. About 51.7% were of Malay ethnicity. The mean score for QOL was 80.17 (21.58). Being a male caregiver (beta = 5.165, p = 0.011) and of Indian ethnicity (beta = -9.163, p = 0.001) were strongly associated with caregiver QOL. Male patients contributed higher QOL scores for the caregivers compared to female patients. There was an inverse relationship among caregiving strain, duration of caregiving, and caregiver QOL. Conclusion: The identification of factors that affect QOL will allow healthcare providers to develop appropriate interventions. It is important that caregivers be in good health so as not to compromise the care they provide to their patients.