Background: In IMbrave050, adjuvant atezo + bev demonstrated a statistically significant and clinically meaningful improvement in recurrence-free survival (RFS) vs active surveillance in patients (pts) at high risk of HCC recurrence following resection or ablation with curative intent. Further, the safety of atezo + bev was generally manageable. Here, we additionally report PRO data from IMbrave050. Methods: IMbrave050 (NCT04102098) enrolled HCC pts at high risk of recurrence following resection or ablation. Pts were randomized to Arm A (atezo + bev) or Arm B (active surveillance). Pts in Arm A received atezo 1200 mg + bev 15 mg/kg IV q3w for a period of one year (17 cycles). Pts in Arm B underwent active surveillance for one year and were eligible to crossover to atezo + bev following independent review facility (IRF) confirmation of recurrence. The primary endpoint was IRF-assessed RFS. Pre-specified exploratory analyses included change from baseline in global health status (GHS)/quality of life (QoL), physical functioning, role functioning, emotional functioning, and social functioning. Clinically meaningful deterioration was defined as a ≥ 10-point decrease. Pts completed the IL42–EORTC QLQ-C30 (reduced) questionnaire at baseline and then at every odd treatment/surveillance visit through Cycle 17. Results: The ITT population included 334 pts in both Arms A and B. With a median follow-up time of 17.4 mo (clinical cutoff date: 21 Oct 2022), IRF-RFS HR was 0.72 (95% CI: 0.56, 0.93; P = 0.0120). In the safety population, Grade 3 or 4 adverse events occurred in 41% of 332 Arm A pts and 13% of 330 Arm B pts. In ITT pts, IL42 completion rates remained ≥ 93% in both arms from baseline through treatment/surveillance Cycle 17. Mean scores at baseline in both arms were high and similar, as measured by the GHS/QoL and physical, role, emotional and social functioning scales. Mean changes from baseline were not considerable through Cycle 17 and were similar between arms as evidenced by overlapping 95% CIs. Pts’ GHS/QoL and functioning was maintained through Cycle 17, with no clinically meaningful deterioration observed at any time. Conclusions: Statistically significant and clinically meaningful improvement in RFS was seen in pts receiving atezo + bev vs active surveillance. Atezo + bev safety was generally manageable, and consistent with the established safety profiles of each therapeutic agent and with the underlying disease. PRO outcome analyses revealed similar overall health-related QoL (HRQoL) and functioning between atezo + bev and active surveillance, and that treating high-risk pts with HCC with adjuvant atezo + bev following procedures with curative intent did not result in a clinically meaningful deterioration in HRQoL or function. Clinical trial information: NCT04102098.