Abstract: OBJECTIVE To explore the imaging changes of limbs long bone infections and bone tumors so as to provide guidance for clinical differential diagnosis. METHODS Totally 82 patients with limbs long bone infections who were treated in hospitals from Jan 2013 to Jan 2016 were chosen as the experimental group, meanwhile, 74 patients with bone tumors were set as the control group.The two groups of patients were treated with X-ray, CT, and MRI examinations, the examination signs were defined, observed, and recorded.The imaging changes and the effects on differential diagnosis were observed and compared between the patients with limbs long bone infections and the patients with bone tumors. RESULTS The tibia, femur, and humerus ranked the top 3 lesion sites among the patients in the experimental group, accounting for 34.15%, 23.17%, and 17.07%, respectively; tibia, femur, and humerus ranked the top 3 lesion sites among the patients in the control group, accounting for 32.43%, 28.38%, and 16.22%, respectively, and there was no significant difference between the two groups.The dead bone, marrow cavity abscess and continuous lamellar periosteal bone ranked the top 3 skeletal change signs among the patients in the experimental group, accounting for 100.00%, 100.00%, and 93.88%, respectively.The Codman triangle, change of femoral medullary cavity, and lesions with clear boundaries ranked the top 3 skeletal change signs among the patients in the control group, accounting for 95.74%, 94.00%, and 87.10%, respectively, and there was significant difference between the two groups (P＜0.05). CONCLUSION The X-ray, CT, and MRI can be used for the differential diagnosis of the limbs long bone infection and bone tumors, which may raise the diagnosis rate and are worthy to be promoted in the hospital.