Objective: The purpose of this study was to describe the caregiver’s proxy-report of the quality of life (QoL) of children with cancer and the main family caregiver’s competence, and to examine the role of said competence and other care-related variables in their proxy-reported QoL of children with cancer. Method: This was a cross sectional, correlation design study conducted with 97 main family caregivers of children between the ages of 8 and 12 years with cancer residing in Colombia. The following variables were collected: main family caregiver and child sociodemographic characteristics (Survey for Dyad Care; GCPC-UN-D), The Pediatric Quality of Life Inventory 4.0 Cancer Module, and the Competence Instrument (caregiver version). Results: The mean of the children’s QoL was 102.0 points, and the caregivers’ competence score was 211.24. Caregiver’s competence ( t = 5.814, p < .01), marital status ( t = 1.925, p < .05), time as a caregiver ( t = 2.087, p < .05), number of hours spent caring for the child ( t = 2.621, p < .05), and caregiver’s previous caring experiences ( t = 2.068, p < .05) were found to influence caregiver’s proxy-report of the QoL of children with cancer. Conclusions: High competence in main family caregivers positively influence caregiver’s proxy-report of the QoL of children with cancer. Study results also suggest that nurses should consider the caregivers’ sociodemographic characteristics such as marital status, time as a caregiver, number of hours spent caring for the child, and caregiver’s previous experiences because those aspects influence main family caregivers’ proxy-report about their children’s QoL.