Objective To explore the application of teaching mode of problem-based learning (PBL) combined with clinical pathway (CP) to the practice teaching of hematological malignancies. Methods Fifty clinical interns of Department of Hematological Internal Medicine were selected and randomly divided into the traditional teaching group (n=25) and PBL combined with CP teaching group (n=25). The traditional teaching group adopted the traditional teaching methods, namely the lecture based learning (LBL) while the PBL combined with CP teaching group adopted the teaching mode of PBL combined with CP. The teaching feedback and results of two groups were compared. Results The evaluation of teaching feedback of the PBL combined with CP teaching group by teachers and students was higher than that of the traditional teaching group and the difference was statistically significant (P<0.05). Comparison of the teaching quality showed that average scores of academic examination (92.95±4.55 vs 84.45±6.28), clinical practical skill (94.25±4.75 vs 87.45±5.84), and ability of case analysis (92.33±5.28 vs 83.65±7.32) were remarkably higher than those of the traditional teaching group and the differences were statistically significant (P<0.01). Conclusion The teaching mode of PBL combined with CP is feasible for the clinical practice teaching of hematological malignancies. It can normalize the diagnosis and treatment, improve the quality of practice teaching, and greatly enhance the learning interest and clinical practice ability of interns.