Objective To investigate the effect of the blending learning based on small private online course (SPOC) in histology.Methods 361 students from grade 2016 and 2017 undergraduate clinical medicine in Harbin Medical University were randomly selected and divided into experimental group and control group. The control group received traditional education, and the experimental group received the blending pathway of education based on SPOC. The learning outcome was evaluated through questionnaire survey and the exam result of students, and the panel discussion of the teachers.Results There was no significant difference between these two groups in test scores(P>0.05). According to the survey in students and teachers, the experimental group was better than the control group in stimulating interest in learning, improving critical thinking, communicating skill and the ability of solving problem(P<0.05). Satisfaction with blending learning based on SPOC reached 97%. Teachers thought it has a significant effect on improving the teacher-student relationship, teaching interests, and occupational pride.Conclusions The blending learning based on SPOC in histology was better than traditional teaching method in the teaching of histology.