The basic leucine zipper and the W2 domain-containing protein 1 (BZW1) plays a key role in the cell cycle and transcriptionally control the histone H4 gene during G1/S phase. Since cellular proliferation rates are frequently dysregulated in human cancers, we identified the characteristics of BZW1 in cancer cells and analyzed its prognostic value in lung cancer patients. By searching public databases, we found that high BZW1 expression was significantly correlated with poor survival rate in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma. Similar trends were also shown in an array comprising NSCLC patient tissue. Knockdown of BZW1 inhibited cell metastatic ability, but did not affect the cell proliferation rate of NSCLC cells. From transcriptomics data mining, we found that coordination between BZW1 and EGFR overexpression was correlated with a worse outcome for lung cancer patients. In summary, BZW1 expression serves as an independent prognostic factor of NSCLC, especially in lung adenocarcinoma. Overexpression of BZW1 in lung cancer cells revealed a novel pathway underlying the induction of lung cancer metastasis.