Objective: Illness cognition is an important predictor of psychological adjustment among breast cancer patients; however, interventions related to illness cognition remain limited. This study aimed to determine the feasibility and effectiveness of a group-based acceptance and commitment therapy (ACT) intervention in improving illness cognition among breast cancer patients undergoing chemotherapy. Methods: A quasi-experimental “time-block” design, with two arms and four assessment time points, was used. Eighty-four patients were recruited from a breast cancer center; 42 patients were assigned to the ACT group and 42 to the health education (HE) group. The ACT group participated in four sessions of group-based ACT intervention in a clinical setting, and the HE group underwent one session of group-based HE. Psychological flexibility, illness cognition, and quality of life were assessed at a pre-intervention time point (T1, baseline), a post-intervention time point (T2, 4 weeks), and two follow-up time points (T3, 8 weeks; T4, 16 weeks). Results: The effects of time (p < 0.001) and the interaction of time with group (p < 0.001) on psychological flexibility, illness cognition, and quality of life were significant. The rate of improvement in the ACT group was greater than in the HE group. Significant intervention effects were observed for psychological flexibility, illness cognition, and quality of life at T2, T3, and T4. Conclusions: The intervention was effective in improving psychological flexibility, illness cognition, and quality of life. However, a randomized controlled trial is needed to confirm the findings of this pilot study. © 2019 Association for Contextual Behavioral Science