PurposeThis study aimed to determine the effectiveness of a Phone-Based Support Program (PBSP) for newly diagnosed women with breast cancer. MethodsA two-group repeated measures randomized controlled trial was designed. Participants included 94 patients aged 18–60 years who were newly diagnosed with breast cancer and undergoing chemotherapy in a tertiary hospital in China. They were randomly assigned to the intervention and the control groups. Participants in the intervention group were enrolled in a four-session PBSP, consisting of four interactive sections: learning, discussion, ask-the-expert, and personal stories, plus the routine care. Outcomes included patients’ self-care self-efficacy, psychological distress (including symptom distress, anxiety, and depression), and quality of life. These were assessed at three time points: pre-intervention (T1), post-intervention (T2), and follow-up (T3) by using the self-care self-efficacy scale, the M.D. Anderson Symptom Inventory, the hospital anxiety and depression scale, and the global health status scale. ResultsAfter completion of the intervention, participants in the intervention group had significantly (p < .001) higher self-care self-efficacy (T2: Mdiff = 11.49, T3: Mdiff = 22.33), better quality of life (T2: Mdiff = 8.18, T3: Mdiff = 17.19), lower symptom distress (T2: Mdiff =−26.68, T3: Mdiff = −54.76), less anxiety (T2: Mdiff = −2.52, T3: Mdiff = −5.11), and less depression (T2: Mdiff = −3.61, T3: Mdiff = −6.71) than those in the control group. ConclusionThese findings indicate that the PBSP is effective. Healthcare professionals, especially nurses, could utilize it to enhance self-care self-efficacy and quality of life, as well as decrease psychological distress among women newly diagnosed breast cancer. RegistrationThe Thai Clinical Trial Registry #TCTR20230321010.