Objective To investigate the effect of quercetin on cell proliferation, migration, and invasion and PI3K/ AKT pathway regulation in the oral cancer cell line Tca-8113. Methods Tca-8113 cells were cultured in vitro and divided into a control group and quercetin ( 50 μmol / L) treatment group. A CCK-8 assay was used to detect cell proliferation; a Transwell assay ( with Matrigel) was used to detect cell migration ( invasion); quantitative real-time polymerase chain reaction was used to detect the expression of PTEN, AKT, FOXO1, and BCL2L11 mRNA; and Western blot was used to detect FOXO1, p-FOXO1, AKT, p-AKT, PTEN, and BCL2L11 protein expression. Results Compared with the control group, the proliferation, migration, and invasion abilities of Tca-8113 cells in the quercetin treatment group were significantly reduced; the PTEN and BCL2L11 mRNA and protein expression levels were significantly up-regulated (P< 0. 05); and the phosphorylated FOXO1 and AKT levels were significantly down-regulated (P< 0. 01). However, there was no significant difference in the AKT and FOXO1 mRNA expression levels between the two groups. Conclusions Quercetin can inhibit the proliferation, migration, and invasion of Tca-8113 cells. In terms of the underlying mechanism, quercetin may promote the expression of PTEN and negatively regulate the PI3K/ AKT pathway to reduce the phosphorylation level of FOXO1, causing an increase in the expression of BCL2L11.