Background and objectives: Colorectal cancer (CRC) is the 2^nd most cause of cancer related death in the world, but early diagnosis ameliorates the survival of CRC. This report directed to identify molecular biomarker signatures in CRC. Materials and Methods: We analyzed two microarray datasets (GSE35279 and GSE21815) to identify common differentially expressed genes (DEGs). We performed functional overrepresentation, pathway enrichment, protein-protein interaction (PPI), reporter biomolecules, survival, and drug repositioning analyses were done on common DEGs. Results: Total 727 up-regulated and 99 down-regulated DEGs were detected. The significantly enriched pathways PI3K-Akt signaling, Wnt signaling, ECM-interaction, cell cycles were identified. The 10 hub proteins (ADNP, CCND1, CD44, CDK4, CEBPB, CENPA, CENPH, CENPN, MYC, and RFC2) were selected as proteomic signatures from PPI network. Analyses revealed 10 reporter transcription factors (ETS1, ESR1, GATA1, GATA2, GATA3, AR, YBX1, FOXP3, E2F4, and PRDM14) and 2 reporter microRNAs (miR-193b-3p and miR-615-3p) as regulatory component. The prognostic power analysis revealed that hub proteins and reporter biomolecules related with worse survival of patients in CRC. Several candidate repositioned drugs including anti-neoplastic and immunomodulating agents were identified using Connectivity map (CMap) and geneXpharma tool. Conclusions: This study presents biomarker signatures at protein and RNA levels with prognostic capability in CRC. We think that the molecular signatures and candidate drugs presented in this study can be potential biomarkers and therapeutic target in CRC.