Background: The health-related quality of life (HRQoL) HRQoL continues to be understudied among family caregivers with chronically ill children especially in developing countries like Malawi. Aim: This study aimed to assess health-related quality of life and determine the sociodemographic factors associated with the health-related quality of life of caregivers of children with lymphoma at a referral hospital in Malawi. Materials and Methods: A cross-sectional study was carried out at a referral hospital in Malawi, and 107 caregivers were recruited. The Medical Outcomes Study Questionnaire 36-Item Short Form was used to collect data which were analysed using SPSS Version 25. Results: All 107 targeted participants were assessed. Both the physical health component and the mental health component mean scores were low (M=50.63, SD=11.86 and M=45.51, SD=11.95, respectively). Time since diagnosis of the child’s cancer accounted for significant differences in both the physical and mental health components’ mean scores (F(2, 104)=5.030, p=0.002 and F(2, 104)=5.030, p=0.006, respectively). The caregivers >41years old, those who were married, those who were employed, and caregivers whose children were diagnosed >12 months were among those more likely to report a better physical health perception compared to those without these characteristics. Conclusion: The health-related quality of life of the caregivers at the referral hospital was severely impaired. The findings suggest that caregivers of children with lymphoma have the potential to develop more serious mental and physical health problems; hence, interventions to mitigate the burden of caring for children with lymphoma are needed.