Glioma is one of the most aggressive and lethal human cancers with a low cure rate. LASP1 plays an oncogenic role in multiple human cancers; however, its role in glioma remains largely unknown. Here, we found that LASP1 was highly expressed in glioma tissue samples. Functionally, knockdown of LASP1 significantly suppressed glioma cell proliferation and migration in vitro and tumorigenicity in vivo. These effects were found to be mechanistically associated with suppression of AKT activity. Furthermore, we identified LASP1 as a direct target of miR-377-3p. Overexpression of miR-377-3p reduced the expression of LASP1 and suppressed the proliferation and migration of glioma cells. Restoration of LASP1 expression in miR-377-3p–overexpressing cells attenuated the inhibition of glioma cell malignancy and reversed the dephosphorylation of AKT. Taken together, our results suggest that LASP1 activates the PI3K/AKT signaling pathway and is downregulated by miR-377-3p during glioma progression. These data provide a new possible therapeutic target in glioma.