Objective The purpose of this study was to explore the mediating effect of intern nurses’ humanistic care quality on self-efficacy and clinical communication ability. Methods Convenience sampling method was used to select 211 intern nurses from six tertiary hospitals in Shanghai from September 2023 to February 2024 as research subjects. A survey was conducted using a general demographic data questionnaire, a general self-efficacy scale, a nursing student clinical communication ability scale, and a nursing humanistic care quality scale. A total of 211 valid questionnaires (100.00%) were collected. Results The study showed that the self-efficacy score of intern nurses was (28.85 ± 3.88) points, the total score of clinical communication ability was (86.01 ± 7.36) points, and the total score of humanistic care quality was (116.74 ± 11.16) points. The predictive effect of self-efficacy on clinical communication ability was significant (t=10.673, P<0.01), and after incorporating humanistic care qualities, the predictive effect of self-efficacy on clinical communication ability was still significant (t=4.685, P<0.01). The indirect effect value was 1.129, the direct effect accounts for 55.98% of total effect, and indirect effect accounts for 44.02%. Conclusions In this study, the quality of humanistic care played a partial mediating role between self-efficacy and clinical communication ability in intern nurses. Therefore, nursing educators should adopt multiple strategies to enable intern nurses to better understand the feelings of patients, improve the quality of humanistic care, to enhance their clinical communication ability.