Background. Long-term health-related quality of life (HRQoL) is an important consideration in planning treatment for individuals with brain tumours. Aim. The current study examined relationships between HRQoL and anatomical location of the lesion in patients 6-24 months post-surgery. Methods. Following left-hemisphere tumour resection, 37 individuals underwent behavioural testing and MRI. A principal component analysis across 10 HRQoL measures identified two components explaining ~62% of the variance: a communication-related and a mood-related component. Three lesion maps were generated per participant capturing (1) the primary resection, (2) the resection plus residual tumour, oedema, and peri-resection treatment effect (resection+), and (3) residual tumour, oedema, and peri-resection treatment effect alone (residual). Relationships between HRQoL components and lesion maps were examined using voxel-wise lesion symptom-mapping as well as general linear models predicting tract- and voxel-wise disconnection severities. Results. Communication-related quality of life was significantly associated with lesions comprising both the resection+ and residual tumour in the left medial inferior parietal lobe. Voxel-wise analyses of white matter disconnection severities revealed significant associations between communication-related quality of life and thalamostriatal fibres for the residual tumour lesions. None of the analyses involving mood-related quality of life or the primary resection lesion maps were significant. Conclusions. The findings highlight the role of the residual tumour, oedema, and peri-resection treatment effects and associated white matter disconnection in communication-related quality of life following treatment.