This article aims to investigate the inhibitory effect and molecular mechanism of sculponeatin A (STA) on triple negative breast cancer (TNBC). MDA-MB-436 and MDA-MB-468 were selected as cell models. The MTT assay, real-time cell analysis (RTCA), and colony formation assay were used to evaluate the effects of different concentrations of STA on the proliferation of TNBC cells. JC-1 staining and Annexin V-FITC/PI double staining combined with flow cytometry were used to measure the effect of STA on the apoptosis of TNBC cells. Western blot was employed to determine the expression changes of apoptosis-related proteins [cysteinyl aspartate-specific proteinase (caspase)-9, caspase-3, and poly-ADP-ribose polymerase (PARP)] and cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein kinase B (AKT) signaling pathway proteins [CIP2A, AKT, phosphorylated (p)-AKT] in TNBC cells after STA treatment. To clarify the function of CIP2A in the action of STA, a CIP2A overexpression or CIP2A knockdown plasmid was transfected into cells, which were then treated with STA. Cell proliferation, apoptosis, and protein expression changes were evaluated by CCK-8, flow cytometry, and Western blot. Further, RT-qPCR and Western blot both showed that STA significantly downregulated the mRNA and protein levels of CIP2A and the protein level of c-Myc. The overexpression of c-Myc antagonized the downregulating effects of STA on the protein and mRNA levels of CIP2A, while the knockdown of c-Myc enhanced this effect. The drug affinity-responsive target stability (DARTS) assay and microscale thermophoresis (MST) assay confirmed the existence of direct binding between STA and c-Myc protein. The results indicated that STA significantly inhibited the proliferation and colony formation and induced the apoptosis of TNBC cells, manifested by an increased apoptosis rate, downregulated precursor protein expression of caspase-9 and caspase-3, and increased PARP cleavage. STA treatment reduced the p-AKT level but did not affect total AKT. Functionally, the knockdown of CIP2A enhanced the STA effects of inhibiting proliferation and inducing apoptosis, while the overexpression of CIP2A produced antagonistic effects. From a mechanism perspective, STA directly targets and binds to c-Myc to downregulate its expression, thereby inhibiting the transcription and translation of CIP2A and ultimately blocking the c-Myc/CIP2A signaling pathway. In conclusion, STA inhibits the malignant progression of TNBC by targeting the c-Myc/CIP2A signaling axis.