We have studied the effect of acute L-glutamine deprivation on the expression oftumor protein 53 (TP53)-related genes such as TOPORS (topoisomerase I binding, arginine/serine-rich, E3 ubiquitin protein ligase), TP53BPI (TP53 bindingprotein 1), TP53TG1 (TP53 inducible gene 1), SESN1 (p53 regulatedPA26 nuclear protein), NME6 (NME/NM23 nucleoside diphosphate kinase 6), and ZMAT3 (zinc finger Matrin-type 3) in glioma cells with ERN1 knockdown. It was shown that blockade of ERN1 finction in U87 glioma cells is induced the expression of RYBP and SESN1 genes, but decreased the expression of TP53BP1, TP53TG1, TOPORS, NME6, genes. Moreover, the expression levels ofRYBPI SESN1, TP53BP1, and ZMAT3 genes is increased in control glioma cells by L-glutamine deprivation condition but blockade of ERN1 signaling enzyme function significantly enhances this effect on the expression all of these genes. At the same time, the ERN1 knockdown eliminates the response TP53TG1 and TOPORS genes to L-glutamine deprivation condition. Results of this investigation clearly demonstrate that the expression most of genes encoding TP53-related factors depends upon acute L-glutamine deprivation condition as well as upon ERN1, the major signaling system of the endoplasmic reticulum stress.