Objective To explore the relevant influencing factors and intervention measures of patients with osteosarcoma. Methods The clinical data of 80 osteosarcoma patients admitted to our hospital from March 2020 to March 2022 were retrospectively analyzed, and all the patients were treated with a comprehensive regimen based on surgery. At 6 months after surgery using cancer patients QoL scale (QLQ-C30), according to QLQ-C30 score and poor quality of life, collect two groups of age, gender, lesion location, culture level, nutritional status, clinical stage, pathological fracture, surgical mode, distant metastasis, sleep quality, family function, coping, first, Logistic regression analysis, obtain independent risk factors affecting the quality of life of osteosarcoma patients. Results The QLQ-C30 score of the 80 months postoperative osteosarcoma patients was scored (76.58 ± 5.14), Twenty-three patients who scored below 70 were classified as a poor QoL group, Fifty-seven patients with 70 points were classified as a good quality of life group; As the univariate factor shows, Nutritional status, clinical stage, pathological fractures, surgical methods, distant metastasis, sleep quality, family function, and coping style are related to the quality of life of patients with osteosarcoma, The difference was statistically significant (P <0.05); Multiple factors show that, Poor nutritional status, clinical stage period, pathological fracture, amputation surgery, distant metastasis, poor sleep quality, low level of family function, and unaccumulation response were the high-risk factors affecting the quality of life of patients with osteosarcoma (P <0.05 and OR> 1). Conclusion Poor nutritional status, clinical stage period, pathological fracture, amputation surgery, distant metastasis, poor sleep quality, low family function level, and unaccumulation response are the high-risk factors affecting the quality of life of osteosarcoma patients, and relevant clinical intervention measures need to be taken as soon as possible to improve the quality of life of osteosarcoma patients.