By screening dozens of reported natural compounds using both wild-type and mutant IDH1 enzymatic assays, we discovered Licochalcone A is a selective inhibitor to the R132C-mutant IDH1 with an IC<sub>50</sub> value of 5.176 μM, and inhibits the proliferation of sarcoma HT-1080 cells with an IC<sub>50</sub> value of 10.75 μM.