Background and Objectives: As one of the most common treatments for breast cancer, mastectomy has adverse effects on the quality of sexual life and sexual functioning in the impacted women. Various strategies have therefore been proposed to resolve their sexual problems. The present study was conducted to determine the effect of sexual rehabilitation using the PLISSIT model in post-mastectomy breast cancer survivors. Materials and Methods: The present quasi-experimental study was conducted on a population of post-mastectomy breast cancer survivors and their husbands. Sample size was calculated as 50 each for intervention and non-intervention groups. The former received sexual counseling based on the PLISSIT model consisting of four levels of intervention: permission, limited information, specific suggestion and intensive therapy, presented in four 90-minute sessions. Data were collected using the Sexual Quality of Life-Female (SQOL-F) questionnaire and the Female Sexual Function Index (FSFI). Results: No significant differences were observed in the mean quality of sexual life scores between the intervention and control groups (P>0.05) before the intervention; however, a significant difference emerged between the groups after the intervention (P<0.01). Thus the mean score for sexual functioning in the intervention group was 26.3±3.76 before and30.0±4.38 after the intervention (P<0.0001). In the control group, however, the difference between the pre- and post-intervention mean scores was not statistically significant (P=0.713). Conclusion: The present study showed that nurses can use the PLISSIT model in conjunction with chemotherapy and radiotherapy to teach coping and problem-solving skills to women with breast cancer and their husbands and to encourage their participation in group programs for expressing their feelings and attitudes about their current sex life and thus help enhance quality of sexual life and sexual functioning in this group.