Objective To design a virtual simulation experimental project for nursing of acute leukemia patients and explore its application effects. Methods From the perspective of students，a virtual simulation experimental project for nursing of acute leukemia patients was constructed，which including four modules：knowledge preview，virtual simulation practice mode，virtual simulation test mode，and experimental evaluation and feedback. The project involved six categories of response actions，namely，safety，communication，assessment，intervention，medication/intravenous management，and effect evaluation. The project was applied to the experimental teaching of leukemia for 78 undergraduate nursing students from the 2020 and 2021 grades at one university. After the teaching，students’ training duration，number of visits，and experimental scores were collected. A self-designed questionnaire was used to invite students to evaluate the system and teaching effects. Results In the practice mode，students visited 3（1，5） times with an online training duration ranging from 29 to 346[53（48，132）] minutes，and the average practice score was（78.34±16.96） points. In the assessment mode，students scored（92.28±4.75） points with an exam duration of （45.09±5.23） minutes. Besides，84.6%（66/78） of students rated “satisfied” or “very satisfied” with the system overall，78.2%（61/78） found the system “easy” or “very easy” to use，and 80.8%（63/78） considered the system “effective” or “very effective” in terms of effectiveness. Between 75.6% and 93.6% of students agreed that the virtual simulation experimental project had several positive teaching effects，including improving the ability to observe leukemia conditions，exercising clinical thinking in leukemia，enhancing nurse-patient communication skills，stimulating interest in learning about leukemia，improving leukemia nursing abilities and strengthening the spirit of humanistic care，and enhancing the level of related operational skills covered in the project. Conclusion The virtual simulation experimental project for nursing of acute leukemia patients is applicable and highly recognized by students for its effectiveness，laying a certain foundation of knowledge and skills for clinical practice in acute leukemia nursing.