Background: Communication is a basic function of human beings, and it could affect nurse interns’ selfefficacy. The aim of the study was to assess the effect of a communication skills training program for nurse interns on their self-efficacy. Subjects and methods: Setting: The study was conducted at Al-Azher University hospitals. Design: A one-group pretest-posttest quasi-experimental study design was used to carry out the study. Subjects: 81 nurse interns. Tools: Data were collected using three tools: a selfadministered questionnaire that included a knowledge questionnaire, a communication skill observation checklist, and a nursing self-efficacy scale. Results: The studied nurse interns’ ages ranged from 23 to 25 years, and all of them were female. Level of knowledge related to communication improved from 44.4% at pre to 91.4% post, and 87.7% at follow-up intervention phase (p<0.001). The level of nurse interns’ communication skills with patients improved from 22.2% at pre to 81.5% at post and 74.1% at the at the follow-up intervention phase (p<0.001). The total level of nurse interns’ communication skills with the health care team improved from 23.5% at pre-intervention to 84% at post-intervention and 77.8% at follow-up intervention (p<0.001). Level of nurse interns' self-efficacy improved from low level at pre to high level at post and follow-up intervention phase (p<0.001). In multivariate analysis, the intervention was a positive predictor of the knowledge score, and this was a positive predictor of the communication skills and nursing self-efficacy scores. Conclusion: The training program in communication skills is effective in improving nurse interns’ knowledge, communication skills, and nursing self-efficacy. Recommendations: The study recommends the application of the developed program to all nurse interns in the study settings every internship year.