Background: The Internet has become a major means of acquiring health information due to the increasing demand for health information and the development of the Internet. However, Internet health information is of mixed quality and may therefore significantly affects health-related behaviour and decisions. The trust of patients in their physicians may potentially change because of health information obtained from the Internet, thereby affecting their compliance to medical diagnoses and treatment. Hence, it is significant to discuss the relationship between Internet health information and patient compliance from the perspective of trust. Objective: This study aimed to discuss the relationship between Internet health information and patient compliance from the dimensions of quality and source through theoretical principle (i.e. cognition-and affect-based trust) and empirical study. Methods: An online survey involving 375 participants from 28 cities in China was conducted to assess the research model, which included two independent variables (i.e. Internet health information quality and source of Internet health information), two mediator variables (i.e. cognition-and affect-based trust) and one dependent variable (i.e. patient compliance). All variables were measured using multiple-item scales from previously validated instruments. The scales' reliability and validity were analysed, demographic analysis was performed and hypotheses were tested using structural equation modelling (SEM). Results: The questionnaire response was 89.6%, and the reliability and validity was acceptable (Cronbach's α = .950 > .700, KMO = .907 > .700, P < .001). This study indicated that the quality and source of Internet health information impacted cognitionand affect-based trust, consequently, patient compliance. In addition, Internet health information source also directly affected patient compliance, and the Internet health information quality was more important than the source of information. Furthermore, cognition-and affect-based trust had significant positive impacts on patient compliance, and cognition-based trust had a significant impact on affect-based trust. Unexpectedly, a nonsignificant relationship between source of Internet health information and affectbased trust was found. Conclusions: The Internet health information quality plays a more important role than the source of information in impacting patient trust, consequently, patient compliance. Therefore, patient compliance should be improved by strengthening the management of Internet health information quality and urging physicians to focus on health websites, and acquire health information from these websites to understand the information accessed by patients and enrich their knowledge structure to show their specialization and reliability in their interaction with patients. Cognition-and affect-based trust directly impact patient compliance. Therefore, physicians can communicate with patients through health websites to allow patients to acquire health informati...