Objective To investigate the effect of pinocembrin ( Pin) on the apoptosis and migration of mouse melanoma B16 cells, and its relationship with the disheveled-associated activator of morphogenesis 2 (DAAM2) / Wnt / β-catenin signaling axis. Methods CCK8 method was used to screen the Chinese medicine monomers that could inhibit the viability of B16 cells in vitro. Cell apoptosis and migration of melanoma B16 cells were detected by flow cytometry and wound healing assay, respectively. Possible core genes of Pin were analyzed by RNA-seq sequencing combined with GEPIA database analysis. Expression levels of DAAM2 and the Wnt / β-catenin signaling pathway-related genes and proteins Axin2, phospho ( p)-glycogen synthase kinase (GSK)-3β, and p-β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction ( qPCR) and Western blot.Reversion experiments were performed by transfection with a DAAM2-overexpression plasmid. A mouse melanoma model was established in vivo, and the mice were then treated with low and high doses (10 mg / kg, 30 mg / kg) of Pin by gavage and melanoma growth was observed. The effects of Pin on DAAM2, Axin2, β-catenin, and p-GSK3β expression in melanoma tissues were detected by Western blot, to clarify its effect on melanoma progression. ResultsPin significantly promoted apoptosis (P<0. 001) and inhibited the migration of B16 cells ( P<0. 01, P<0. 001).RNA-seq and GEPIA analysis suggested that DAAM2 was a key target. Pin significantly reduced DAAM2 mRNA and protein expression, as shown by qPCR and Western blot ( P<0. 05, P<0. 01, P<0. 001), and down-regulated expression levels of the Wnt / β-catenin signaling pathway-related proteins p-GSK3β, p-β-catenin, and Axin2 (P<0. 001). High-dose Pin significantly inhibited melanoma growth and weight in mice in vivo, and reduced DAAM2,axin2, β-catenin, and p-GSK3β expression in tumor tissues (P<0. 05, P<0. 01), while DAAM2 overexpression reversed the effects of Pin on the DAAM2 / Wnt / β-catenin signaling axis. Conclusions Pin can promote the apoptosis of melanoma cells, inhibit their migration, and inhibit melanoma growth in mice by down-regulating the DAAM2 / Wnt / β-catenin signaling axis.