In this study, we compared the registration effectiveness of 4D cone-beam computed tomography (CBCT) and 3D-CBCT for image-guided radiotherapy in 20 Stage IA non-small-cell lung cancer (NSCLC) patients. Patients underwent 4D-CBCT and 3D-CBCT immediately before radiotherapy, and the X-ray Volume Imaging software system was used for image registration. We performed automatic bone registration and soft tissue registration between 4D-CBCT or 3D-CBCT and 4D-CT images; the regions of interest (ROIs) were the vertebral body on the layer corresponding to the tumor and the internal target volume region. The relative displacement of the gross tumor volume between the 4D-CBCT end-expiratory phase sequence and 4D-CT was used to evaluate the registration error. Among the 20 patients (12 males, 8 females; 35-67 years old; median age, 52 years), 3 had central NSCLC and 17 had peripheral NSCLC, 8 in the upper or middle lobe and 12 in the lower lobe (maximum tumor diameter range, 18-27 mm). The internal motion range in three-dimensional space was 12.52 +/- 2.65 mm, accounting for 47.8 +/- 15.3% of the maximum diameter of each tumor. The errors of image-guided registration using 4D-CBCT and 3D-CBCT on the x (left-right), y (superior-inferior), z (anterior-posterior) axes, and 3D space were 0.80 +/- 0.21 mm and 1.08 +/- 0.25 mm, 2.02 +/- 0.46 mm and 3.30 +/- 0.53 mm, 0.52 +/- 0.16 mm and 0.85 +/- 0.24 mm, and 2.25 +/- 0.44 mm and 3.59 +/- 0.48 mm (all P < 0.001), respectively. Thus, 4D-CBCT is preferable to 3D-CBCT for image guidance in small pulmonary tumors because 4D-CBCT can reduce the uncertainty in the tumor location resulting from internal motion caused by respiratory movements, thereby increasing the image-guidance accuracy.