Based on the high expression of folic acid (FA) receptors in triple-negative breast cancer cells, we encapsulated licochalcone A (LCA) in FA-modified polyethylene glycol-poly(lactic-co-glycolic) acid nanoparticles (NPs) for enhanced targeting and antitumor activity. In vitro experiments on 4T1 cells showed that NPs with FA modification exhibited excellent performance, including inhibition of cell proliferation, reduction of 50% inhibitory concentration values of LCA, and activation of reactive oxygen species production, thereby inhibiting cell proliferation. This drug delivery system promotes drug uptake by tumor cells and significantly improves drug delivery efficiency. Regarding relevant in vivo experiments in tumor-bearing mice, we further demonstrated that NPs with FA modification have significant tumor-targeting effects, as shown by drug penetration and small animal imaging experiments. Target-modified NPs loaded with LCA significantly inhibited tumor growth and prolonged survival in mice. Histological analysis further demonstrated the positive effect of the preparation in reducing lung and liver metastasis lesions. Our study highlights that FA-modified NPs can effectively deliver LCA to the tumor site, enhancing the potential application of LCA to inhibit tumor proliferation and metastasis, and providing new strategies and possibilities for treating triple-negative breast cancer.