〔Abstract〕 Objective To explore the clinical significance and mechanisms of chromatin licensing and DNA replication factor 1(CDT1) in lung adenocarcinoma). Methods The gene expression samples of lung adenocarcinoma tissue and normal lung tissue were downloaded from the TCGA database, and perform differential analysis, GO analysis, independent prognosis analysis, and correlation analysis with immunotherapy using R language. CDT1 expression in lung adenocarcinoma and normal tissues was detected by PCR in clinical samples. The changes of cell proliferation and cycle in si-CDT1 knockdown group and si-NC control group were detected by flow cytometry. The invasive ability of each group was detected by Transwell. The expressions of CDT1, TPX2 and p53 in each group were detected by Western blot. Results The TCGA data analysis revealed CDT1 as a differentially expressed gene. GO analysis indicated that CDT1 was closely associated with the cell cycle. The high expression of CDT1 in lung adenocarcinoma tissues was validated in clinical samples. CDT1 could serve as an independent factor for predicting the prognosis of lung adenocarcinoma and had predictive value for immunotherapy in lung adenocarcinoma. Knockdown of CDT1 resulted in a significant decrease in cell proliferation ability compared to the control group, and cells were noticeably arrested in the G1 phase. Transwell assay results demonstrated a significant reduction in invasive capacity in the CDT1 knockdown group. Knockdown of CDT1 led to a significant decrease in TPX2 expression and a significant increase in p53 expression, while overexpression of CDT1 yielded the opposite effect. Conclusion Results demonstrate the elevated expression of CDT1 in lung adenocarcinoma, its association with prognostic significance, and its impact on lung adenocarcinoma's occurrence and development by influencing TPX2 and p53.