A study conducted from September to October 2022 with 1,900 medical students from a university in Guangzhou, China, explored the factors influencing self-efficacy in online learning. The study utilized the Online Learning Self-Efficacy Questionnaire, the Depression-Anxiety-Stress Scale (DASS-21), and a self-administered questionnaire assessing sociodemographic characteristics and self-evaluation of learning effectiveness. Statistical analyses using SPSS 25.0 and AMOS 25.0, including univariate and multi-factor analyses, were performed to examine the data. The results indicated that the average online learning self-efficacy score among the students was (56.83±7.97). Structural equation modeling revealed that male students (p < 0.005), those with higher per capita monthly household income (p < 0.001), and students who assessed their online learning effectiveness positively (p < 0.001) exhibited significantly higher self-efficacy. In contrast, students experiencing higher levels of depression (p < 0.001), anxiety (p < 0.001), and stress (p < 0.001) had significantly lower self-efficacy for online learning. The study concluded that gender, per capita family income, self-assessment of learning effectiveness, and mental health conditions such as depression, anxiety, and stress are key factors influencing medical students’ self-efficacy in online learning. Based on these findings, it is recommended that university teachers focus on improving online teaching management, provide additional support for financially disadvantaged students, and balance online and offline learning. Encouraging collaboration, fostering motivation, and introducing strategies like flipped classrooms and increased online interaction are crucial for enhancing students’ self-efficacy and improving academic outcomes. Addressing students’ negative emotions through these methods can maximize online learning effectiveness for medical students. © 2025 Taylor & Francis Group, LLC.
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