In a previous study, we have shown that shortening of telomeres by telomerase inhibition sensitized cancer cells to cisplatinum, slower their migration, increased DNA damage and impaired DNA repair . In the following study, we present a network model combining microRNA and proteomic profiling attempting to decipher the molecular mechanism underlying the effect of shortened telomeres on the obtained phenotype of cancer cells . The microRNA and proteomic data were used for a network model construction, which provided us with several nodal candidates that may potentially mediate the shortened-telomeres dependent features. These protein expressions were experimentally validated, supporting their potential central role in this system . In this article, we delineate the full proteomic data and a microarray analyses performed on cells with shortened telomeres compared to their cognate parental intact telomere cells. The data is attached as excel files. In principle, clarifying the mechanism behind telomere shortened phenotype may facilitate novel therapeutics development and may also obviate the time consuming process of telomere shortening achieved by telomerase inhibition.