The liver is able to orchestrate a regenerative process to compensate the loss of functional tissue. Resection of 70% of liver parenchyma (partial hepatectomy, PH) in mice is a well stablished model to analyze the mechanisms underlying liver regeneration. Three phases can be defined in liver regeneration: sensitization of hepatocytes to mitogenic factors, proliferative response and regeneration termination. To dissect in detail liver regeneration mechanisms after PH we have generated a dynamic framework integrating the changes in protein abundance and phosphorylation along the three phases of the process. Proteomic and phosphoproteomics analysis in the starting regeneration phase shows a total of 4300 proteins identified, of which 2800 quantified being 219 differentially regulated in the PH / sham contrast (215 up-regulated and 4 down-regulated, qvalue <0.05) with 24 peptides differentially phosphorylated (21 up-regulated and 3 down-regulated, qvalue <0.05). Principal cellular pathways were deregulated during the sensitization phase, such as Inflammation, sirtuin Signaling, PXR/RXR,NRF2-mediated Oxidative Stress Response, Planar cell polarity (PCP) signaling, PI3K/AKT and RhoA signaling. Moreover, transcriptional factors including HNF4 (Hepatocyte nuclear factor 4 alpha) that plays a central role in liver differentiation and FGF19 (Fibroblast growth factor 19) which regulates the synthesis of bile acids through the FGFR4 / Klotho-β complex in the liver, were also impaired. The activation of FGF19 was confirmed since the expression of its target genes (Cyp7a1, Idh3a, Cytc, Atp5b, Pepck, G6pase and Pgc) was significantly modified. Our preliminary data provide an integrated framework to understand in detail the mechanisms associated to liver regeneration and may prove to be translatable to humans and benefit liver diseased patients.