Objective: To investigate the role and mechanism of COL11A1 in lung adenocarcinoma migration and invasion. Methods: Surgical pathological tissues of 4 patients with lung adenocarcinoma admitted to the Affiliated Hospital of Guizhou Medical University from September to November 2020 were used. Immunohistochemical methods were used to identify lung adenocarcinoma tissues, para-cancerous tissues and parallel transcriptome sequencing. Genetic prognostic analysis was conducted by TCGA and GTEx databases.The expression level of COL11A1 gene in lung adenocarcinoma and adjacent tissues was detected by Western blotting.The primary human lung adenocarcinoma cells cultured. The COL11A1 siRNA was transfected into primary human lung adenocarcinoma cells, then the transcriptome sequencing of differential genes was performed,and KEGG enrichment analysis of differential gene enrichment pathway was conducted. Protein expression and phosphorylation were detected by Western blot method. Cell migration was detected by scratch healing test. Cell proliferation was detected by CCK8 method and invasion ability was detected by Transwell method. Results: Ten differentially expressed genes were screened by transcription sequencing in lung adenocarcinoma. Prognostic analysis of single gene showed that COL11A1 gene expression level was correlated with survival rate ( P <0.001). The expression of COL11A1 in lung adenocarcinoma was higher than that in adjacent tissues by Western blot ( P <0.001). Transcriptome sequencing of COL11A1 siRNA transfection into primary human lung adenocarcinoma cells showed that differential genes were concentrated in PI3K-akt pathway. The expression of tumor suppressor gene PTEN in siRNA transfection group was significantly higher than that in control group and negative transfection group by Western blot. The expression of Aktp-Akt 473 p-Akt 308 p-PTENp-PDK1p-c-Rafp-GSK-3 β was down-regulated (all P <0.05).Compared with the negative control group, the ability of migration, proliferation and invasion of primary human lung adenocarcinoma cells in siRNA transfection group decreased (all P <0.05). COL11A1 regulates PI3K/Akt/GSK-3 β pathway to promote migration and invasion of primary human lung adenocarcinoma cells. Conclusion: COL11A1 regulates PI3K/Akt/GSK-3 β pathway to promote migration and invasion of primary human lung adenocarcinoma cells.