To evaluate the antiviral effects of Xiao'er Resuqing Oral Liquid on coxsackievirus A16(Cox A16) infection models in vivo and in vitro.Methods:Three-day-old BALB/c mice were intraperitoneally injected with Cox A16 to establish a hand-foot-mouth disease(HFMD) model in BALB/c mice.Three different doses of Xiao'er Resuqing Oral Liquid ［62，31，and 15.5 mL/(kg·d)］ were designed for both prophylactic and therapeutic administration evaluations.In the prophylactic administration experiment，the infection level，survival days，mortality rate，and life extension rate of the mice were observed and recorded.In the therapeutic administration experiment，real-time polymerase chain reaction(PCR) was used to detect the viral load in the hind limb muscles，and hematoxylin-eosin(HE) staining was performed to observe the pathological changes in the hind limb muscle and brain tissues.In the in vitro experiment，the cytopathic effect(CPE) method was used to assess the inhibitory effects of Xiao'er Resuqing Oral Liquid on Cox A16，Cox B4，and Cox B5 viruses.Real-time PCR was used to detect the Cox A16 viral load in vitro.Results:Xiao'er Resuqing Oral Liquid at high，medium，and low doses significantly prolonged the survival days of the mice(P<0.01 or P<0.05).Xiao'er Resuqing Oral Liquid at high and medium doses significantly reduced the mortality rate and clinical infection score(P<0.01).Xiao'er Resuqing Oral Liquid at medium and low doses significantly reduced the viral load in the hind limb muscles(P<0.01 or P<0.05).Xiao'er Resuqing Oral Liquid at high and medium doses significantly improved the histopathological changes and pathological scores in the hind limb muscles(P<0.01 or P<0.05)，while that at medium dose significantly improved the histopathological changes and scores in the brain tissues(P<0.05).The in vitro experiment showed that Xiao'er Resuqing Oral Liquid had a significant inhibitory effect on Cox B5，Cox A16，and Cox B4 enteroviruses.Conclusion:Xiao'er Resuqing Oral Liquid has good prophylactic and therapeutic effects on the Cox A16 infection model in BALB/c mice and may exert its effects by inhibiting viral replication.