Abstract Background One of the most frequently diagnosed oncological diseases among young persons is Low-grade glioma (LGG). More than 80% of LGGs progress to higher-grade tumors always lethal to a patient. LGG is an extremely heterogeneous group of primary glial brain tumors with a quite variable rate of recurrence, survival, and response to treatment. Thus a study of new biomarkers associated with disease progression and patient outcome is useful to improve patient management. Genes involved in key cellular processes, e.g., apoptosis, are promising prognostic and predictive cancer markers. Phosphatidylserine (PS) plays an essential role in apoptosis signaling. Several studies suggested PS is dysregulated in the tumor microenvironment and offends the development of anti-cancer immune response. The scramblases PLSCR1 and XKR8 allegedly could be associated with the progression and outcome of LGG since they could be involved in the development of immunity via regulation of PS activity by its bidirectional translocation in the plasma membrane. Thus this study was aimed to evaluate associations of PLSCR1 and XKR8 with disease-free and overall survival of LGG patients. Methods Gene expression values and clinical information of 530 LGG patients were downloaded from TCGA Low-Grade Glioma study using the public resource CBioPortal. According to gene expression values (RNA Seq V2 RSEM) patients were divided into two groups: with downregulated ( mean) PLSCR1 or XKR8 gene. The Kaplan-Meier procedure and Log-Rank test were used for survival analysis. All calculations were performed in the integrated development environment - RStudio. Results It was shown the LGG patients with upregulated PLSCR1 (p = 2.54e-14) and XKR8 (p = 7.33e-15) gene had worse disease prognosis than other patients. Similar associations were seen in the study of LGG progression, where patients with upregulated PLSCR1 (p = 7.75e-07) and XKR8 (p = 5.59e-10) gene had a higher risk of cancer recurrence. Conclusions Consequently, PLSCR and XKR8 genes could be considered as new prognostic biomarkers of LGG progression and outcome. Legal entity responsible for the study Research Laboratory "Biomarker". Funding The work was performed according to the Russian Government Program of Competitive Growth of KFU. Disclosure All authors have declared no conflicts of interest.