Consistent with the in vitro results, caffeine significantly inhibited G6PDH enzymatic activity, p-STAT3 signaling activation, and cyclin E, NOX4, and p47-phox (NOX2 regulatory subunit) protein expression, and upregulated the expression of SOD2 protein, in xenografted RCC tumor tissues. The gene discussed is H6PD; the disease is renal cell carcinoma.