Summary Proinfl ammatory cytokines contribute to the progression of muscle wasting caused by ubiquitin-proteasome-dependent proteolysis. We have previously demonstrated that isofl avones, such as genistein and daidzein, prevent TNF-␣-induced muscle atrophy in C2C12 myotubes. In this study, we examined the effect of dietary fl avonoids on the wasting of muscle. Mice were divided into the following four groups: vehicle-injected (control) mice fed the normal diet (CN); tumor-bearing mice fed the normal diet (TN); control mice fed the isofl avone diet (CI); and tumor-bearing mice fed the isofl avone diet (TI). There were no significant differences in the intake of food or body weight gain among these four groups. The wet weight and myofi ber size of gastrocnemius muscle in TN signifi cantly decreased, compared with those in CN. Interestingly, the wet weight and myofi ber size of gastrocnemius muscle in TI were nearly the same as those in CN and CI, although isofl avone supplementation did not affect the increased tumor mass or concentrations of proinfl ammatory cytokines, such as TNF-␣ and IL-6, in the blood. Moreover, increased expression of muscle-specifi c ubiquitin ligase genes encoding MAFbx/Atrogin-1 and MuRF1 in the skeletal muscle of TN was signifi cantly inhibited by the supplementation of isofl avones. In parallel with the expression of muscle-specifi c ubiquitin ligases, dietary isofl avones signifi cantly suppressed phosphorylation of ERK in tumor-bearing mice. These results suggest that dietary isofl avones improve muscle wasting in tumor-bearing mice via the ERK signaling pathway mediated-suppression of ubiquitin ligases in muscle cells.