Enterovirus 71 (EV71) infections can cause hand, foot, and mouth disease with severe neurological complications. Because no clinical drug is available for treating EV71 infections, developing an efficient antiviral medication against EV71 infection is crucial. This study indicated that 6-bromo-2-[1-(2,5-dimethylphenyl)-5-methyl-1H-pyrazol-4-yl] quinoline-4-carboxylic acid (BPR-3P0128) exhibits excellent antiviral activity against EV71 (EC50 = 0.0029 μM). BPR-3P0128 inhibits viral replication during the early post infection stage, targets EV71 RNA-dependent RNA polymerase and VPg uridylylation, and also reduces viral RNA accumulation levels and inhibits viral replication of EV71.