High mobility group protein B1 (HMGB1) plays an important role in a number of clinical conditions, such as autoimmunity, cardiovascular disease and cancer. Evidence suggests that HMGB1 is critical in the development and progression of numerous types of tumor. However, the underlying molecular mechanisms for the HMGB1-mediated progression and metastasis of lung cancer have not yet been elucidated. In this study, we investigated the role of HMGB1 in lung adenocarcinoma and the mechanisms by which it contributes to carcinogenesis and metastasis. We demonstrated that there was an increase in the expression of HMGB1 in primary cancer tissues compared to the matched adjacent non-cancerous tissues. The expression levels of TOB1 in the normal human bronchial epithelial (HBE) cell line and 10 lung cancer cell lines were determined by reverse transcription-PCR (RT-PCR). The results revealed that HMGB1 expression increased in 8 cell lines compared with the HBE cell line. The A549 and NCI-H1975 cells were transfected with HMGB1 recombinant plasmid. We discovered that the overexpression of HMGB1 promoted cell growth and metastasis in the 2 cell lines. Further investigation revealed that exogenously expressed HMGB1 enhanced the activation of p38 and Erk1/2, in addition to the expression of nuclear factor (NF)-κB. We propose that HMGB1 functions as a tumor promoter and that it regulates the proliferation and invasion of lung cancer cells by modulating the activation of the Erk1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathways.