Background: Because glioblastoma is currently incurable, the goal of therapy is the optimization of the patient’s quality of life (QOL). Tumor location is critical in screening surgical candidates, yet the impact of tumor location on QOL has never been demonstrated. By using a novel computer-driven algorithm, we set out to investigate the impact of tumor location on QOL. Methods: The tumors of fourty consecutive glioblastoma patients were segmented and the Euclidian distance between 90 brain regions and each tumor’s margin was calculated and correlated to the patients’ self-reported QOL as measured by the SNAS questionnaire. Results: QOL was statistically associated with proximity to three areas: the right para-hypocampal gyrus, the right posterior cingulate cortex and the right postcentral gyrus. We postulate that the adverse relation between proximity to these areas and QOL results from disruption in large-scale networks involved in high-order functions such as visuospatial memory. While harder to detect with a bedside clinical examination, such deficits are likely more impactful on QOL than those related to the motor cortex or Broca’s area. Conclusions: Tumor proximity to right parietooccipital region are associated with decreased QOL. This should be considered in the management strategies of glioma patients.