Informal caregivers play a crucial role in dialysis care but may experience significant burden, potentially affecting both caregiver and patient outcomes. Research on caregiver burden and health-related quality of life (HRQoL) and the relation to patient-reported outcomes (PROs) is lacking. Therefore, we aimed to (i) describe informal caregivers' experienced burden and HRQoL and (ii) investigate how these are related to dialysis patients' HRQoL and symptoms. We conducted a cross-sectional study at dialysis initiation with 202 adult informal caregiver-dialysis patient dyads. Caregiver burden was measured with the Self-Perceived Pressure from Informal Care (SPPIC) questionnaire, HRQoL with the 12-item Short Form Health Survey (SF-12), and symptom number and burden with the Dialysis Symptom Index (DSI). Data were analysed using linear and logistic ordinal regression. Around 38% of caregivers experienced moderate to high burden. Patients' lower mental HRQoL [adjusted odds ratio (aOR)=0.95, 95% confidence interval (CI) 0.92; 0.99], higher symptom number (aOR=1.07, 95% CI 1.02; 1.12) and higher symptom burden (aOR=1.03, 95% CI 1.01; 1.04) were associated with greater odds of higher caregiver burden. Patients' lower mental HRQoL (β=0.30, 95% CI 0.15; 0.46), higher symptom number (β=-0.55, 95% CI -0.78; -0.31) and higher symptom burden (β=-0.17, 95% CI -0.25; -0.10) were also associated with a lower mental HRQoL in caregivers. We show that a third of caregivers feel moderate to high burden and that caregiver burden is associated with patients' mental HRQoL and symptoms. These findings highlight the importance of recognizing informal caregivers and the nature of their burden.