Objective To establish a model of malignant transformation of human cells in vitro to study the lung cancer induced by radon and cigarette smoke. Methods The immortalized human bronchial epithelial cells BEAS-2B were divided into control group( C ), radon group ( Rn), cigarette smoke group (Sm) and combined group (Rn-Sm). Cells were planted onto transwell membrane one day before exposure and were directly exposed to radon and cigarette smoke pumped in a gas inhalation box. After the exposure cells were trypsinized into dishes for further growth and malignancy transformation phenotype was detected in order to compare the effects due to radon and cigarette smoke exposure. Results BEAS-2B cells showed malignantly transformed phenotype by exposure to radon and cigarette smoke. A series of sequential steps emerged among transformed cells, including altered growth kinetics, resistance to serum has changed from 0. 31 ± 0. 18 to 1.92 ± 0. 27,2. 03 ± 0. 14,2.95 ± 0. 60, and anchorage-independence growth increased from (0.01 ±0.02)% to (4.89 ±0.30)%,(8.36 ±0.50)%,(11.74 ±0.69)%.After being subculture for 20 generations, cell apoptosis of the fifth generation cells exposed to radon,cigarette smoke and both was significant decreased from ( 11.76 ± 0. 17 ) % to (4. 62 ± 0. 42 ) %、 ( 8.63 ±0. 15 )%、 (3.68 ± 0. 33 )%. Conclusions BEAS-2B cells could be malignancy transformed by radon and cigarette smokein vitro, which could be used as a cell model in lung bronchial carcinogenesis.