Abstract： Objective To analyze the influencing factors of cone-beam CT (CBCT) imagine registration in lung cancer. Methods From Mar. 2007 to Dec. 2007, 20 patients with lung cancer were treated with IGRT. The imagines of CBCT were collected from 6 to 19 fractions during the patients' radiotherapy. To compare the difference of set-up errors between the two groups according to the distance from the lesion in lung to the centrum. At the same time, CBCT imagines from the first, middle and the last fraction of these patients' radiotherapy were registrated in bone and grey methods by four doctors. The difference of set-up errors between different doctors and registrated methods were compared. Results The mean values of set-up errors were ＜2 mm in the two groups without significant difference (x:-1.31mm vs 0. 10 mm (t=0. 07,P=0.554);y:1.24 mm vs 1.37 mm (t=0. 05,P=0. 652);z: - 1.88mm vs -1.26mm (t= -0. 12,P=0.321)). The mean values of set-up errors were ＜ 1.3 mm in four doctors and registrated methods without significant difference, for bone registration,x: -0. 05 mm, -0. 01 mm,0. 05 mm, -0.12 mm and -1.31 mm ( F=-0.01,P=0.887) ;y:0.56 mm,0.35 mm,0.51 mm and 0.43 mm (F= -0.01,P=0.880);z: -1.16 mm, -1.20 mm, -0.88 mm and -1.03 mm (F= -0.04,P=0. 555 ), for grey registration ,x: -0.32 mm, -0.341 mm, -0.395 mm and - 0.37 mm(F=-0.01, P=0.874);y:0.34 mm,0.54 mm, -0.04 mm and 0.27 mm (F= -0.03,P=0.622);x:-1.12 mm,- 1.15 mm, - 1.13 mm and - 1.04 mm (F=0. 00,P=0. 812). Conclusions With the same registrated box and imagine quality, the location of the lesions in lung, registred methods and different doctors are not the influencing factors for CBCT imagine registration.