AIM: To study the effect of NEDD8-conjugating enzyme UBE2F on lung adenocarcinoma metastasis. METHODS: The expression of UBE2F in lung adenocarcinoma was analyzed using TIMER2.0, UALCAN and HPA databases. Kaplan-Meier Plotter database was used to analyze the relationship between UBE2F expression and survival rate of lung adenocarcinoma. A UBE2F-knockout lung adenocarcinoma cell line was constructed using CRISPR/Cas9 technology, and a UBE2F-knockout lung adenocarcinoma metastasis model was constructed in nude mice to verify the effect of UBE2F knockout on lung adenocarcinoma metastasis. The effects of UBE2F knockout on invasion and migration of lung adenocarcinoma cells were examined by cell scratch assay and Transwell invasion and migration assays. The effect of down-regulated UBE2F expression on snail expression, a key marker of epithelial-mesenchymal transition (EMT), was detected by Western blot and Real time PCR. RESULTS: Multiple database analysis showed that UBE2F was highly expressed in lung cancer, and Kaplan-Meier Plotter analysis showed that high expression of UBE2F in lung adenocarcinoma had better prognosis than low expression. In vivo experiments showed that compared with control group, the number of nodules metastasized on the lung surface of nude mice after UBE2F knockout was significantly increased (P<0.05). Cell scratch assay and Transwell assay showed that UBE2F enhanced the migration and invasion ability of lung cancer cells after knockout, and the difference were statistically significant (P<0.05). Western blot and Real time PCR results indicated that the level of EMT transcription factor snail protein and mRNA increased after UBE2F knockout. CONCLUSION: In lung adenocarcinoma cells, UBE2F down-regulation leads to Snail accumulation and promotes invasion and metastasis of lung adenocarcinoma cells.