Guanylate-binding protein 7 (GBP7) belongs to the GBP family, which plays key roles in mediating innate immune responses to intracellular pathogens. Thus far, GBP7 has been reported to be a critical cellular factor against bacterial infection. However, the relationship between GBP7 and influenza A virus (IAV) replication is unknown. Here, we showed that GBP7 expression was significantly upregulated in the lungs of mice, human peripheral blood mononuclear cells (PBMCs), and A549 cells during IAV infection. Using the CRISPR-Cas9 system and overexpression approaches, it was found that GBP7 knockout inhibited IAV replication by enhancing the expression of IAV-induced type I interferon (IFN), type III IFN, and proinflammatory cytokines. Conversely, overexpression of GBP7 facilitated IAV replication by suppressing the expression of those factors. Furthermore, GBP7 knockout enhanced IAV-induced nuclear factor-κB (NF-κB) activation and phosphorylation of stat1 and stat2; overexpression of GBP7 had the opposite effect. Our data indicated that GBP7 suppresses innate immune responses to IAV infection via NF-κB and JAK-STAT signaling pathways. Taken together, upon IAV infection, the induced GBP7 facilitated IAV replication by suppressing innate immune responses to IAV infection, which suggested that GBP7 serves as a therapeutic target for controlling IAV infection. So far, few studies have mentioned the distinct function of guanylate-binding protein 7 (GBP7) on virus infection. Here, we reported that GBP7 expression was significantly upregulated in the lungs of mice, human PBMCs, and A549 cells during IAV infection. GBP7 facilitated IAV replication by suppressing the expression of type I interferon (IFN), type III IFN, and proinflammatory cytokines. Furthermore, it was indicated that GBP7 suppresses innate immune responses to IAV infection via NF-κB and JAK-STAT signaling pathways. Taken together, our results elucidate a critical role of GBP7 in the host immune system during IAV infection.