INTRODUCTIONHepatocellular carcinoma (HCC), the primary form of hepatic carcinoma and a prevalent malignant tumor, is associated with a poor prognosis (Gentile et al., 2020). Various risk factors, such as cirrhosis, autoimmune hepatitis, HBV or HCV infection, nonalcoholic fatty liver disease, and alcohol abuse, contribute to HCC progression (Fujiwara et al., 2018; Kim and Han, 2012; Wang and Deng, 2023). The aggressive proliferation, metastatic capacity, and high drug resistance rates of HCC cells are major factors contributing to their invasive behavior (Llovet et al., 2021; Villanueva, 2019). Despite significant progress in clinical HCC treatment, the prognosis for patients remains grim due to rapid progression and early recurrence (Cai et al., 2022; Donadon et al., 2016; Wang and Wei, 2020). Thus, it is crucial to develop new drugs and identify novel therapeutic targets for HCC treatment.Forkhead box proteins constitute an evolutionarily conserved family of transcriptional regulators. Among them, forkhead box M1 (FOXM1) is known to be expressed in proliferating cells and associated with the activation of the mitotic program (Zuppo et al., 2023). FOXM1 plays a crucial role in cancer progression, influencing various steps such as Epithelial-Mesenchymal Transition (EMT), cell proliferation, migration, and premetastatic niche formation (Park et al., 2011; Raychaudhuri and Park, 2011; Zhang et al., 2017). In the context of HCC, FOXM1 has been found to be upregulated and contributes to the progression of HCC by directly regulating the expression of KIF4A (Hu et al., 2019). Notably, carfilzomib has demonstrated effectiveness in inhibiting FOXM1 expression in AFP-positive HCC cells, leading to the inhibition of tumor growth (Li et al., 2022). These findings underscore the significance of FOXM1 as a potential therapeutic target in HCC treatment.The canonical Wnt/β-catenin signaling pathway plays a pivotal role in regulating cell growth, differentiation, and migration (Gao et al., 2018; Liu et al., 2022). Central to this pathway is the β-catenin protein, which, upon translocation into the nucleus, interacts with the TCF/LEF-1 transcription factor complex to activate the expression of Wnt target genes, including C-myc, CyclinD1, MMP2, MMP7, and MMP9 (Yu et al., 2021). Dysregulation of this signaling cascade contributes to tumorigenesis and metastasis.β-Sitosterol, one of the most prevalent phytosterols, is widely distributed in vegetable oils, nuts, and traditional Chinese medicinal plants (Babu and Jayaraman, 2020). β-Sitosterol, one of the most prevalent phytosterols, is widely distributed in vegetable oils, nuts, and traditional Chinese medicinal plants (Khan et al., 2022). Numerous studies suggest that β-sitosterol hinders the malignant behavior of cancer cells by inhibiting their proliferation and migration, inducing apoptosis, and interfering with cellular metabolism (Awad et al., 2008; Bae et al., 2021). Despite the significant role of β-sitosterol in various diseases, its impact on HCC and the underlying mechanism remains unexplored. Thus, the objective of this study was to investigate the inhibitory effect of β-sitosterol on HCC progression by regulating the FOXM1-mediated Wnt/β-catenin signaling pathway.