Objective Image-guided radiation therapy(IGRT)was performed to investigate the intrafractional body motion and identify the relevant influencing factors during hypofractionated radiotherapy for malignant pulmonary tumors. Methods A total of ninety-six patients with malignant pulmonary tumors receiving hypofractionated radiotherapy in Jiangsu Cancer Hospital were enrolled in this clinical trial. The kilo-voltage cone beam CT(kV-CBCT)was acquired prior to each fraction and matched to the planning CT images to correct the set-up errors. CBCT was performed immediately after the end of treatment to evaluate the intrafractional variation in the mediolateral,anteroposterior and craniocaudal dimensions.The relationship between relevant influencing factors and intrafractional variation was analyzed using multivariate linear regression. Results In the anteroposterior and craniocaudal directions,the intrafractional positioning errors were reduced along with the increase of ordinal number of fraction(P= 0.000). In the mediolateral direction, the intrafractional positioning errors were increased along with the longer duration of hypofractionated radiotherapy(P=0.010).The intrafractional positioning errors were decreased over larger body weight(P=0.003).The intrafractional positioning errors were significantly increased when vacuum bag and thermoplastic film were utilized for fixation(P= 0.009). Conclusions Certain intrafractional positioning errors occur during hypofractionated radiotherapy. Relevant influencing factors differ in different directions. Relevant influencing factors should be modified to reduce intrafractional positioning variation and improve the treatment accuracy.