<p>Lung cancer has the highest incidence and mortality rates among all malignant tumors worldwide, with poor treatment outcomes and a high risk of postoperative recurrence. Currently, more than 50% of lung cancer cases are lung adenocarcinoma, which is characterized by early metastasis, recurrence, and therapeutic challenges. However, lung adenocarcinoma underlying nosogenesis mechanisms remain unclear. miRNAs are small non-coding RNAs that play crucial roles in regulating cell differentiation, proliferation, apoptosis, and other processes. They exert biological functions by suppressing the expression of target genes and have emerged as key players in cancer diagnosis, treatment, and prognosis evaluation. Numerous studies have shown that miR-542-3p is aberrantly expressed in various tumors and can either promote or inhibit the development and progression of multiple malignancies. This study aims to investigate the expression of miR-542-3p in lung adenocarcinoma and its effects on the biological behavior of lung adenocarcinoma cells, as well as to analyze the relationship between miR-542-3p, TTF1, and the MAPK pathway, with the goal of identifying novel therapeutic targets for lung adenocarcinoma. The results demonstrate that miR-542-3p is lower expressed in lung adenocarcinoma, where it directly regulates TTF1 expression and subsequently inhibits the MAPK signaling pathway indirectly via TTF1 downregulation, thereby reducing the proliferation, migration, and invasion capabilities of lung adenocarcinoma cells and suppressing tumor growth. This study is the first to reveal the critical role of the miR-542-3p/TTF1/MAPK regulatory axis in lung adenocarcinoma cell proliferation, migration, invasion, and tumor growth.</p>