Background: Our previous study showed that SUMO1 expression is closely related to progression in non‐small cell lung cancer (NSCLC); however, the function of SUMO1 in NSCLC has not yet been well elucidated.Methods: SUMO1 was enhanced or silenced in two NSCLC cell lines by using either forced SUMO1 expression or short hairpin RNA against SUMO1 lentiviral vectors, respectively. The biological functions of SUMO1 in NSCLC were investigated through colony‐formation, cell proliferation, and invasion assays, and cell cycle analysis. NF‐κB expression was detected in the overexpressed and silenced SUMO1 cell lines. Immunohistochemistry was used to detect an association between SUMO1 and NF‐κB in the cancer and adjacent tissues of 168 patients with lung cancer.Results: Overexpressed SUMO1 promoted the proliferation rate, colony formation ability, invasion, and NF‐κB expression in an A549 cell line. Conversely, SUMO1 depletion inhibited the cell growth rate, colony formation ability, invasion, and NF‐κB expression in a Calu‐1 cell line. SUMO1 expression was significantly correlated with NF‐κB expression in lung adenocarcinoma and squamous carcinoma patients (r > 0.5, P < 0.001).Conclusion: Our results provide evidence that SUMO1 promotes the proliferation and invasion of NSCLC cells by regulating NF‐κB.