Objective To investigate whether a stable and reliable hyperuricemia model can be established in mice with an ICR background via a triple-modeling method ( combined potassium oxazine, hypoxanthine, and 30% yeast paste), and to evaluate the effect of the positive drug febuxostat on the model. Methods A hyperuricemia model of ICR mice was established using a single drug or double- or triple-drug combinations. Serum uric acid and creatinine concentrations, xanthine oxidase (XOD) and urate oxidase (UOX) activity, and uric acid transporter (URAT)1, glucose transporter (Glut)9, anion transporter (OAT)1, and ATP-binding box subfamily G member (ABCG)2 mRNA levels were detected to evaluate whether the hyperuricemia model was formed successfully. Results The serum uric acid levels of ICR mice were not significantly changed by potassium oxazine alone, as they showed an increase but were not significantly different to those of the 30% yeast paste diet or hypoxanthine combined groups. Serum uric acid levels in the triple administration group were significantly increased at 7 days (P<0. 01), while XOD enzyme activity had increased(P<0.01) and UOX enzyme activity decreased (P<0. 001) at the same timepoint. There were increased expression levels of URAT1 and Glut9 (P<0. 05, P< 0. 001), and decreased expression levels of OAT1 and ABCG2 (P<0. 001). During dynamic monitoring, the blood uric acid levels of triple administration-induced ICR mice peaked at 7 days. In addition,triple administration-induced hyperuricemia in ICR mice was sensitive to the positive drug febuxostat, which caused a significant decrease in blood uric acid levels ( P< 0. 001). Conclusions A hyperuricemia model in ICR mice can be stably induced by triple administration for 7 days.