Objective: To investigate the perioperative nursing strategies of patients with malignant tumor of bone received total knee arthroplasty, and put forward nursing strategies in order to reduce complications after joint replacement, improve the surgical curative effect and to improve the life quality of patients. Methods: One hundred and twenty patients diagnosed with knee malignant bone tumors who need total knee arthroplasty in our hospital were completely randomly divided into I group and II group. The patients in the I/II group received conventional clinical nursing, while the patients in the II group received special nursing intervention. The Ennking Musculoskeletal Tumor Rating Scale (MSTS) score, the incidence of postoperative complications, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Pittsburgh sleep quality index (PSQI) score were evaluated. Results: In the II group, the MSTS score was better than I group, the incidence of complications including infection, deep vein thrombosis, knee joint stiffness, muscle atrophy was significantly lower than I group (P<0.05). SDS, SAS, PSQI score in the experimental group was superior to I group (P<0.05). Conclusion: The special perioperative nursing of patients with malignant tumor of bone received total knee arthroplasty can effectively reduce the incidence of complications, the curative effect and improve the patients’ quality of life.