Background and objectives: There are alternative and complementary approaches for general health issues and palliative care for women with breast cancer. This study aimed at evaluating the effectiveness of acceptance and commitment therapy (ACT) on psychological hardiness, social isolation, and loneliness of women with breast cancer. Methods: This was a quasi-experimental study with a pretest-posttest design. The study population consisted of all women with breast cancer who had been referred to the oncology ward of Shohada Tajrish Hospital in Tehran (Iran) in 2020. Thirty subjects were enrolled via purposive sampling and then assigned to an experimental group (n=15) and a control group (n=15). The experimental group received eight sessions of ACT interventions (90 minutes a session), and the control group did not receive any intervention. The subjects were followed-up for eight weeks after the last ACT session. Data were collected using the Lang and Goulet Psychological Hardiness Scale, Social Isolation Questionnaire, and the UCLA Loneliness Scale. The collected data were analyzed using repeated measures ANOVA. Results: The mean age of subjects and mean duration of marriage were 34.23±6.12 years and 8.46±5.14 years, respectively. Based on the findings, the mean scores of psychological hardiness (p=0.005), social isolation (p=0.001), and loneliness (p=0.001) differed significantly between the study groups in the posttest stage. Conclusion: According to the results, it seems that ACT is effective in increasing psychological hardiness and reducing social isolation and loneliness of women with breast cancer.