The key signaling networks regulating glioma cell proliferation remain poorly defined. The leucine-richrepeat containing G-protein coupled receptor 4 (Lgr4) has been implicated in intestinal, gastric, and epidermalcell functions. We investigated whether Lgr4 functions in glioma cells and found that Lgr4 expression wassignificantly increased in glioma tissues. In addition, Lgr4 overexpression promoted while its knockdown usingsmall interfering RNA oligos inhibited glioma cell proliferation. In addition, Wnt/β-catenin signaling was activatedin cells overexpressing Lgr4. Therefore, our results revealed that Lgr4 activates Wnt/β-catenin signaling toregulate glioma cell proliferation.