Raloxifene decreased cell volume compared with vehicle group. The next day after Hep-G2 cancer cells injected, the mice were randomized to give daily oral dosages of 15 mg/kg of Raloxifene or vehicle control for 19 days and tumor volumes were determined every other day (A). After tumors harvested, weighed every tumor by electronic scale (B) and determined the volumes of tumors (C). Raloxifene inhibited P-STAT3 but not total STAT3, and induced caspase-3 cleavage in mouse xenografts in vivo (D). Raloxifene also inhibited STAT3 phosphorylation, decreased the expression of Bcl-2 and induced apoptosis as shown by IHC staining (E). Raloxifene (15 mg/kg) pretreated for 24 hours and IL-6 injected for another 2 hours in nude mice, then P-STAT3 of liver tissues was detected by western blot (F). Raloxifene suppressed the phosphorylation of STAT3 induced by IL-6 in liver tissues of nude mice, which indicated Raloxifene could inhibited IL-6/STAT3 signaling in vivo with one dose of 15 mg/kg.