As a result of enrollment expansion, increasing numbers of students are entering into medical school in China. This combined with a shortage of teachers, means that the learning environment typically consists of a large classroom setting with traditional lecture-based learning (LBL) as the major mode to teaching and learning. In this article, we investigate the preferences for hybrid problem-based learning (hybrid-PBL) or LBL in a large classroom setting. Two hundred five second-year undergraduate students in Third Military Medical University were randomly divided to two groups. The hybrid-PBL group contained 101 students and was taught by hybrid LBL (60%) and tutor-less PBL(40%) in a large classroom. The LBL group consisted of 104 students and was taught by LBL in a large classroom too. Postteaching performance was assessed by multiple choice questions, short-essay questions, and case-analysis questions, while the students' teaching preferences and satisfaction were assessed by questionnaires. Analysis of the results of both groups in the examination of biochemistry revealed significantly higher scores on short-essay questions and case-analysis questions in the hybrid-PBL group. Students considered hybrid-PBL to be an effective learning method and favored it over the lecture format. Furthermore, students reported positive effects of hybrid-PBL in terms of additional learning resources, critical thinking, and fun learning experiences. These results suggest that hybrid-PBL is better than the traditional LBL method at improving students' basic knowledge and problemsolving skills. Students preferred hybrid-PBL and were satisfied with it. The tutor-less PBL pattern in a large classroom setting may be feasible in Chinese medical schools. China like many other countries has a shortage of doctors, as a result there has been a significant increase in the number of students entering medical school. At the same time there has been little increase in the amount of teachers. Together these factors result in traditional lecture-based learning (LBL) in a large classroom (over 100 students) as the major mode of teaching and learning in Chinese medical school [1]. Although there are ways to liven up LBL and strategies to make it more effective, it is mostly passive learning [2]. Lectures usually do not stimulate learners to construct explanatory models and to elaborate when acquiring new information, whereas modern theories of the learning and cognition emphasize the importance of active learning.Over the past two decades, there has been a steady increase in the number of medical colleges with a problembased learning (PBL) curriculum [3]. The educational value and impact of using small group learning, a student-centered approach, and PBL have all been supported by both practice and research [4][5][6]. Today, experts in medical education largely agree that there are differences in the effects of PBL as compared with LBL. PBL is often favored over conventional education by both students and teachers. There is evidence whi...