Licochalcone A (LicA), a major active component of licorice, has been reported to exhibit various pharmacological actions. The purpose of this study was to investigate the anticancer activity of LicA and detail its molecular mechanisms against ovarian cancer. SKOV3 human ovarian cancer cells were used in this study. Cell viability was measured using a cell counting kit-8 assay. The percentages of apoptotic cells and cell cycle arrest were determined by flow cytometry and Muse flow cytometry. The expression levels of proteins regulating cell apoptosis, cell cycle, and the signal transducer and activator of transcription 3 (STAT3) signaling pathways were examined using Western blotting analysis. The results indicated that LicA treatment inhibited the cell viability of SKOV3 cells and induced G2/M phase arrest. Furthermore, LicA induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspases and cytoplasmic cytochrome c. Additionally, LicA caused a dramatic decrease in STAT3 protein levels, but not mRNA levels, in SKOV3 cells. Treatment with LicA also reduced phosphorylation of the mammalian target of rapamycin and eukaryotic translation initiation factor 4E-binding protein in SKOV3 cells. The anti-cancer effects of LicA on SKOV3 cells might be mediated by reduced STAT3 translation and activation.