Obesity markedly increases the risk of colorectal cancer. Recently, the preventive effects of edible mushroomson triglyceride elevation and visceral fat accumulation have been reported. Here, the effects of Pleurotus eryngii(Eringi) and Hypsizygus marmoreus (Bunashimeji) on azoxymethane (AOM)-induced aberrant crypt foci (ACF;precancerous lesions) in the colorectums of mice fed a high-fat diet were examined. Eringi (ER) and Bunashimeji(BU) mushroom powder samples were used. Six-week-old male C57BL/6J mice received an intraperitonealinjection of AOM (10 mg/kg) once a week for two weeks, and were sacrificed and dissected at 6 weeks after thestart of the experiment. After the initiation of the experiment, they received a normal diet (ND), high-fat diet(HFD), HFD + ER (1 or 5% of diet), or HFD + BU (1 or 5% of diet). As a result, body and fat weights weresignificantly lower in the 5% ER and BU groups than in the HFD group. Liver triglyceride levels were alsosignificantly lower in the 5% ER and BU groups. Total liver cholesterol levels were significantly lower in the5% ER group. The numbers of ACF (especially large ACF) showed strong inhibitory effects in both ER and BUgroups. Measurement of the cell proliferation marker Ki-67 labeling index in the colonic mucosa demonstratedmore significant suppression in both ER and BU groups than in the HFD group. These results suggest that thesimultaneous intake of ER and BU may inhibit colorectal tumorigenesis in HFD-fed mice.