The clinical research methodology course focuses on cultivating practical abilities in clinical research design, but the traditional teaching method focuses on knowledge, which is difficult to achieve the expected effects. The online-offline hybrid teaching method helps to cultivate practical abilities through diversified, dynamic, and cross spatial teaching. This study took the clinical research methodology course for graduate student of Capital Medical University as an example, to describe the design and implementation process of this teaching method in this kind of course, and to evaluate its effectiveness by process assessment and questionnaire survey. After the course, the scores of theoretical knowledge [(24.0±1.9) to (18.1±4.7)] and research design elements [(8.6±1.9) to (4.9±2.7)] were higher than those before the course, and the scores of clinical research protocols [(77.2±16.2) to (54.9±21.7)] and research proposal presentation slides [(90.6±2.9) to (83.4±4.2)] were also significantly increased (all P<0.05). Out of 64 students, 60(93.8%) believed that this teaching method could improve their clinical research design ability, and the average satisfaction score was (18.1±0.7). The results showed that the online-offline hybrid teaching method can increase the students′ theoretical knowledge level and improve their practical abilities of clinical research design, and favorable learning effect has been achieved.