A recombinant analog of the human SLURP-1 protein, rSLURP-1, effectively inhibits the growth of carcinomas by interaction with the α7-type nicotinic acetylcholine receptor. Recently, rSLURP-1 inhibition of glioma growth in vitro was shown by the authors; however, the action of rSLURP-1 was not studied. Here, we showed that rSLURP-1 selectively inhibits the growth of U251 MG glioma cells, but not of normal astrocytes, and controls glioma cell migration. In addition, rSLURP-1 induces cell cycle arrest in the G2/M phase in U251 MG glioma cells, but does not result in apoptosis. Incubation of U251 MG cells with rSLURP-1 causes inhibition of phosphorylation of ERK, p38 MAPK, and AKT kinases, whose activation contributes to the progression of gliomas. At the same time, rSLURP-1 does not affect the activity of JNK kinase. Thus, rSLURP-1 is an endogenous protein promising for the development of drugs based on it for the treatment of not only carcinomas but also gliomas.