The purpose of this study was to investigate the role of lncRNA ENST0000000454471 in lung adenocarcinoma progression and tumor immune escape, and to analyze the protein structure and biological function of HDAC8. Various experimental techniques were used in this study, including real-time quantitative PCR (qPCR) to detect the difference in lncRNA ENST0000000454471 expression between lung adenocarcinoma tissue and normal lung tissue. Cell experiments included cell proliferation, migration and invasion experiments to evaluate the effect of lncRNA ENST0000000454471 on the behavior of lung adenocarcinoma cells. Molecular biological techniques such as chromatin immunoprecipitation (ChIP) and co-immunoprecipitation (Co-IP) were used to investigate the interaction between lncRNA ENST0000000454471 and HDAC8. The protein structure was analyzed by X-ray crystallography and molecular dynamics simulation. Cell experiments showed that overexpression of lncRNA ENST0000000454471 promoted the proliferation, migration and invasion of lung adenocarcinoma cells, and inhibitors of HDAC8 could reverse these effects. Further molecular mechanism studies showed that lncRNA ENST0000000454471 regulates the expression of several genes related to tumor progression and immune escape through interaction with HDAC8. Protein structure analysis revealed the active sites and regulatory regions of HDAC8, providing a structural basis for understanding its biological function.