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SARS-CoV-2 triggered the global COVID-19 pandemic, posing a severe threat to public health worldwide. The innate immune response in cells infected by SARS-CoV-2 is primarily orchestrated by type I interferon (IFN), with <i>IFN-β</i> exhibiting a notable inhibitory impact on SARS-CoV-2 replication. <i>FHL2</i>, acting as a docking site, facilitates the assembly of multiprotein complexes and regulates the transcription of diverse genes. However, the association between SARS-CoV-2 and <i>FHL2</i> remains unclear. In this study, we report for the first time that SARS-CoV-2 infection in Caco2 cells results in the upregulation of <i>FHL2</i> expression, while the virus’s N proteins can enhance <i>FHL2</i> expression. Notably, the knockdown of <i>FHL2</i> significantly amplifies SARS-CoV-2 replication in vitro. Conversely, the overexpression of <i>FHL2</i> leads to a marked reduction in SARS-CoV-2 replication, with the antiviral property of <i>FHL2</i> being independent of the cell or virus type. Subsequent experiments reveal that <i>FHL2</i> supports <i>IFN-β</i> transcription by upregulating the expression and phosphorylation of IRF-3, thereby impeding SARS-CoV-2 replication in cells. These findings highlight <i>FHL2</i> as a potential antiviral target for treating SARS-CoV-2 infections.