mRNA expression-based stemness index (mRNAsi) has been used for prognostic assessment in various cancers, but its application in lung adenocarcinoma (LUAD) is limited, which is the focus of this study. Low mRNAsi in LUAD predicted a better prognosis. Eight genes () associated with mRNAsi were screened to establish a risk model. The differentially expressed genes between the high and low risk groups were mainly enriched in the metabolism, cell cycle functions pathway. The low risk score group had higher immune cell scores. Patients with lower TIDE scores in the low risk group had better immunotherapy outcomes. In addition, risk score was effective in assessing drug sensitivity of LUAD. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) data showed that eight genes were differentially expressed in LUAD cell lines, and knockdown of reduced the invasion and migration ability of LUAD cells. This study designed a risk model based on the eight mRNAsi-related genes for predicting LUAD prognosis. The model accurately predicted the prognosis and survival of LUAD patients, facilitating the assessment of the sensitivity of patients to immunotherapy and chemotherapy.