Cancer is a chronic and life-threatening disease that causes complications to the patients diagnosed with it as well as to those who were taking care of them; i.e. the caregivers who normally are family members of the patient. Cancer caregivers experience burden and stress during the period of caregiving which contributes to their quality of life (QOL). However, there is scarce literature on the QOL of gastrointestinal cancer caregivers in the local population. The purpose of this study is, therefore, to determine the health-related quality of life (HRQOL) of male and female caregivers and identify contributing factors to their caregiving. This cross-sectional study was conducted in three major tertiary government hospitals in the Klang Valley. Systematic random sampling was used to recruit the main caregivers of gastrointestinal cancer patients. The inclusion criteria for the caregivers were respondents aged 18 and above, Malaysian, able to understand and read Bahasa Melayu, free from any diagnosed cancer. A total of 323 respondents completed the validated questionnaire on HRQOL from October 2017 to April 2018. Data were analysed using independent t-test and chi-square tests. In the sample population, the majority of patients were females compared to males (68.1% vs 31.9%). The mean HRQOL score for females was 77.66 (SD=21.36) while the mean HRQOL for males was 85.52 (SD=21.16). Data shows that males had a better quality of life in comparison to females. The HRQOL scores were significantly different according to gender, t=3.09, mean difference=7.85(SD=2.54), 95%Cl 2.85,12.85. p value=0.002. Factors that were significantly different between males and females were: relationship between the caregiver and the patient (p-value=0.001); education level (p value=0.019); employment status (p value=<0.001), marital status (p value=0.048), household income (p value=0.021) and presence of disease (p value=0.015). These findings indicate that gender affects caregiving. This implies that health care providers should acknowledge the role of gender in caregiving. This is also a significant factor to guide policymakers in improving the existing healthcare system for caregivers.