BACKGROUND: The medical education system in mainland China faces numerous challenges and the lack of learner-centered approaches may contribute to passive learning and reduced student engagement. While problem-based learning (PBL) is common in Western medical schools, its feasibility in China is questioned due to cultural differences. This systematic review aims to summarize the application of PBL in medical education in mainland China based on existing literature, as well as to identify the challenges and opportunities encountered in its implementation. METHODS: A systematic literature review was conducted using electronic databases, including MEDLINE, Cochrane Library, EMBASE, Web of Science, Wan fang and CNKI databases. Grey literature sources were explored using Google Scholar. The search was limited to articles that include at least one English abstract up to May 1st, 2023. The inclusion criteria were studies that reported the use of PBL in medical education in mainland China. RESULTS: A total of 21 articles were included in the final analysis. The findings indicate that PBL is a well-adopted and effective learning method in most medical education, especially for developing critical thinking, problem-solving, and teamwork skills. However, the application of PBL in mainland China is limited due to various challenges, including faculty resistance, inadequate resources and cultural barriers. To effectively address these challenges, it is essential to provide faculty training, develop appropriate assessment methods to evaluate student progress within the PBL framework and create conducive spaces and resources that support collaborative learning and critical thinking. CONCLUSION: The utilization of PBL in mainland China holds potential for enhancing medical education. However, its successful implementation requires significant efforts to address the identified challenges. It is crucial to engage stakeholders in a collaborative effort to promote the application of PBL and ultimately improve the quality of medical education in mainland China.