The ethanol disturbs the cell cycle, transcription, translation, protein folding, cell wall, membranes, and many Saccharomyces cerevisiae metabolic processes. Long non-coding RNAs (lncRNAs) are regulatory molecules binding onto the genome or proteins. The number of lncRNAs described for yeast is still scarce, and little is known concerning their roles in the system. There is a lack of knowledge concerning how lncRNAs are responsive to the ethanol tolerance in yeast and whether they act in this tolerance. Hence, by using RNA-Seq data from S. cerevisiae strains with different ethanol tolerance phenotypes, we found the severe ethanol responsive lncRNAs. We modeled how they participate in the ethanol tolerance by analyzing lncRNA-protein interactions. The results showed that the EtOH tolerance responsive lncRNAs, in both higher tolerant and lower tolerant phenotypes, work on different pathways: cell wall, cell cycle, growth, longevity, cell surveillance, ribosome biogenesis, intracellular transport, trehalose metabolism, transcription, and nutrient shifts. In summary, lncRNAs seems to interconnect essential systems modules to overcome the ethanol stress. Finally, here we also found the most extensive catalog of lncRNAs in yeast.