Zhi‐Shang‐Feng Granules are used in the clinical treatment of influenza to relieve headaches, chills and fever, bronchitis, nasal congestion, neuralgia and other symptoms. To decipher the components responsible for therapeutic effects of Zhi‐Shang‐Feng g ranules against influenza virus, an analytical method based on high‐performance liquid chromatography coupled with Q exactive focus hybrid quadrupole orbitrap high resolution mass spectrometry was developed and the chemical profile of Zhi‐Shang‐Feng granules was characterized. Then, the identified components were used to conduct network pharmacological analysis and determine the potential mechanism of Zhi‐Shang‐Feng Granules. As a result, 177 compounds were putatively identified through comprehensive analysis by liquid chromatography coupled with high‐resolution mass spectrometry, of which 23 compounds were unambiguously confirmed with reference standards. Components in Zhi‐Shang‐Feng Granules were found to specifically act on different enzymes, G‐protein‐coupled receptors, ion channels and transporters in the immune, endocrine, nervous, and circulatory systems. The potential mechanism was related to several biological processes, including cell growth and death, pattern recognition receptor signalling, signalling by interleukins, and lipid metabolism. The combination of chemical profile characterization and network construction provided useful insight into the overall chemical composition of Zhi‐Shang‐Feng granules and revealed their potential anti‐infection, anti‐inflammatory and immunoregulatory mechanisms against influenza virus infected disease.