Gelsolin-like actin-capping protein (CapG), a ubiquitous actin-binding protein, has been shown to play a critical role in regulating the migration ability of cells. In this study, we investigated CapG expression in lung cancer cell lines under hypoxia and evaluated the effect of CapG on the migration ability of these cells. We also analyzed the expression of CapG in a total of 75 patients with lung adenocarcinoma by immunohistochemistry. Our results showed that hypoxia increased the expression of CapG in the human lung cancer cell lines, A549 and H358. Knockdown of CapG expression with small interfering RNA led to a decrease in the migration ability of these cell lines. These results indicate that CapG expression is upregulated in lung cancer cell lines under hypoxia and that CapG may contribute to the migration ability of lung cancer cells. Moreover, the excised lung adenocarcinoma tissues showed significantly increased immunoreactivity for CapG, compared to the adjacent tumor-free tissues. Importantly, overexpression of CapG is significantly associated with male sex (χ(2) = 5.195, p = 0.033) and lymph node metastasis (χ(2) = 5.58, p = 0.021). Likewise, CapG overexpression was observed with advanced tumor stages (III and IV, 16/31), compared with early tumor stages (I and II, 14/44), but the difference was not statistically significant. These results suggest that overexpression of CapG may be associated with progression of lung adenocarcinoma. In conclusion, CapG may be a promising target for therapy and a potential biomarker for predicting the prognosis of lung adenocarcinoma.