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Background: Paclitaxel (Taxol) is a widely used anti-cancer chemotherapeutic drug for many cancer types.Previously, multiple studies focused on identifying cancer-specific paclitaxel responsive regulatory elements and signatures in particular type of cancers.Here we integrated DNA Methylation and gene expression profiling data to test whether there are shared gene modules and signatures across multiple types of cancer.Methods and Results: The promoter CGI methylation and mRNA expression profiles of multiple types of cancer were integrated to identify the epigenetically regulated genes, by selecting genes which show significant negative correlation between its expression level and promoter CGI methylation.The Cox multivariate regression analysis was adopted to screen genes which are significantly associated with survival times of Paclitaxel treated patients.The overlap signature genes across multiple types of cancers were investigated in human protein-protein interaction networks.We demonstrated that these shared gene modules enriched in gene networks related to cell adhesion, tight junction pathways, synthesis of methionine adenosyltransferase, cell cycle progression and apoptosis.Finally, by combining above features and constructing an SVM classifier, we demonstrated that the consensus gene modules could be used to classify the patient outcomes in various types of cancer.Conclusions: We demonstrated that epigenetically regulated genes and pathways is a common feature related to clinical outcome of paclitaxel treatment in multiple types of cancer .