Exploring the anti-tumor active components of Pholidota cantonensis, the optimal compound was screened out via CCK-8 cytotoxicity assay, and the apoptosis-inducing effect of the active compound on bladder cancer 5637 cell was observed using confocal laser scanning microscopy. The effect of the compound on the invasion ability of 5637 cell was detected using the transwell assay, and the expression levels of proteins related to epithelial-mesenchymal transition (EMT) and proliferation were assessed by western blot. Twelve compounds were isolated from P. cantonensis, respectively coelonin (1), orchinol (2), lusianthridin (3), shancidin (4), isoshancidin (5), 2-hydroxy-4,7-dimehoxy-9,10-dihydrophenanthrene (6), 2-hydroxy-4,7-dimehoxyphenanthrene (7), flavanthrinin (8), blestriarene A (9), ochrone A (10), ephemeranthoquinone (11), and densiflorol B (12). Among the isolates， compounds 1 and 3-10 were identified from the investigated plant species for the first time. Compound 1 inhibited bladder cancer cells in a dose-dependent manner and induced cell apoptosis. Concurrently, it significantly upregulated epithelial cadherin (E-cadherin), downregulated Vimentin and neural-cadherin (N-cadherin), and promoted the expression of zona occludens 1(ZO-1) and desmoplakin (DSP), indicating that the epithelial-mesenchymal transition (EMT) process was reversed. Furthermore, compound 1 likely mediated its anti-proliferative and pro-apoptotic effects by inhibiting extracellular regulated protein kinases (ERK) phosphorylation.