Background: Adenocarcinoma is characterized by high infiltration and negative growth, which is easy to invade the walls of blood vessels and lymphatic vessels. The function of the stem cell population is to control and maintain cell regeneration. Therefore, it is necessary to study the prognostic value of stem cells in LUAD.Methods: Stem cells signature construction relies on the univariate, least absolute shrinkage operator (LASSO) and multivariate Cox regression analysis. Risk plot, Kaplan-Meier analysis and the area under ROC (AUC) are verified the accuracy of the signature in GEO (GSE20319 and GSE42127) and TCGA cohort respectively. What's more, to further improve persuasiveness, we conducted nomogram, drug efficacy analysis, immune infiltration analysis, and compared the relationship between mRNA stem cell index (mRNAsi) and signature.Result: The patients were divided into two groups via the cutoff of risk score; it can be seen that the low-risk group has better survival. The robust signature that contains ten stem cells is independent prognostic factors for LUAD (C6orf62, DNER, NELL2, LATS2, LGR5, PTPRO, LRIG1, PABPC1, NT5E and SET). The nomogram showed that 1-year (0.805), 3-year (0.773), and 5-year (0.765) survival rates of the signature we constructed were all greater than 0.7, indicating that our signature was very feasible.Conclusion: The signature can be used as a reliable and convenient tool for lung adenocarcinoma.