Suraxavir marboxil (GP681) is an antiviral drug inhibiting the polymerase acidic protein (PA) of RNA polymerase, of influenza. It has shown therapeutic activity against influenza A and B virus infections in preclinical studies. In this multicenter randomized, double-blind, placebo-controlled, phase 3 trial, we aimed to investigate the efficacy and safety of single-dose suraxavir marboxil (40-mg oral dose) in otherwise healthy outpatients aged 5-65 years with uncomplicated influenza unaccompanied by severe issues. From 28 July 2022 to 31 October 2023, 591 outpatients aged 5-65 years with uncomplicated influenza underwent randomization in 46 research centers in China and were randomly assigned in a 2:1 ratio to receive suraxavir marboxil (40 mg) or placebo within 2 days of symptom onset. The primary outcome was time to alleviation of influenza symptoms (TTAS) (from the start of treatment until body temperature returned to 37.2 °C or less and all seven influenza symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) resolved for at least 21.5 h) within 15 days by treatment. The secondary endpoints included virological indicators, system and respiratory symptoms, PA variant mutation and adverse events. The median TTAS was significantly shorter in the group that received suraxavir marboxil compared to the placebo group (42.0 h versus 63.0 h, P = 0.002). Suraxavir marboxil was associated with more rapid decrease in viral load from baseline than placebo by 1 day after administration, with a mean change of -2.2 ± 1.3 compared to -1.3 ± 1.7 log