The effects of the element fluorine on the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathway has a significant role in regulation of intracellular molecular mechanisms. NRK-52E rat kidney epithelial cell line was selected as the material of the study. NaF was used as the fluorine source in the study. The NaF dose was determined with the MTT assay. The NaF concentrations were determined as the proliferation concentration of 10 mu M and IC25 (2250 mu M) and IC50 (4250 mu M) for 24 h. In the study, the erb-b2 receptor tyrosine kinase 2 (ERBB2), phosphoinositide-3-kinase (PI3K), Protein kinase B (PKB,Akt), Mammalian target of rapamycin (mTOR), and the Tumor protein 53 (TP53) genes were considered as the target genes. NaF concentration was administered on the cells. Total mRNA was isolated. mRNAs were turned into cDNA. The expression levels of the target genes were determined by RT-qPCR method. According to the results obtained in the study, the low NaF concentration increased the expression levels of the ERBB2, PI3K, and Akt genes, while the higher concentrations did not significantly affect these levels. The expression of mTOR decreased at all given concentrations. The expression of the TP53 gene did not change at the low concentration, while it increased at the high concentrations. Based on the results, it may be stated that fluorine may inhibit the kinase enzymes in the PI3K/Akt pathway. In summary, in the pathogenesis of the cell damage caused by fluorine in the NRK-52E cell line, the PI3K/Akt/mTOR pathway is an important signal pathway.