Background Computed tomography (CT)-guided percutaneous lung biopsy is usually performed by helical scanning. However, there are no studies on radiation dose, diagnostic accuracy, image quality, and complications based on axial scan mode. Purpose To determine radiation dose, accuracy, image quality, and complication rate following an ultra-low-dose (ULD) protocol for CT-guided lung biopsy in clinic. Material and Methods A total of 105 patients were enrolled to receive CT-guided lung biopsy. The use of an ULD protocol (axial scan) for CT-guided biopsy was initiated. Patients were randomly assigned to axial mode (Group A) and conventional helical mode (Group B) CT groups. 64-slice CT was performed for CT-guided pulmonary biopsy with an 18-G coaxial cutting biopsy needle. The radiation dose, accuracy, image quality, and complication rate were measured. Results Ninety-seven patients were selected for the final phase of the study. There was no significant difference between the two groups for pulmonary nodule characteristics ( P > 0.05). The mean effective dose in group A (0.077 ± 0.010 mSv) was significantly reduced relative to group B (0.653 ± 0.177 mSv, P < 0.001). There was no significant difference in accuracy, image quality, and complication rate ( P > 0.050) between the two modes. Conclusion An ULD protocol for CT-guided lung nodule biopsy yields a reduction in the radiation dose without significant change in the accuracy, image quality, and complication rate relative to the conventional helical mode scan.