Although the expression levels of total xylose-binding proteins (XBPs) were up-regulated significantly in the activated hepatic stellate cells (HSCs), however, their denomination, distribution, and functions in HSCs were uncharted.Here, 70 XBPs from the activated LX-2 and 64 XBPs from the quiescent LX-2 were isolated, identified and annotated.A total of 30 XBPs were up-regulated (all fold change≥1.5, p≤0.05) and 14 XBPs were down-regulated (all fold chang≤0.67, p≤0.05) in the activated LX-2.The XBPs were localized at the cytoplasm and cytoplasmic membrane in HSCs and cirrhotic liver tissues by cy/histochemistry.The XBPs (i.e., PDIA6 and CFL2) responsible for the regulation of protein binding were up-regulated, and those (i.e., TUBB and MX1)responsible for the regulation of catalytic activity were up-regulated in the activated LX-2.Then, 2 candidates (e.g., PDIA6 and APOA1) were selected for further verification in the sera of hepatitis B virus induced liver fibrosis/cirrhosis patients (HB)using western blotting and serum microarrays.Assessments of PDIA6 and APOA1 as biomarker candidates show a higher discrimination (AUC=0.8985, p<0.0001) relative to APOA1 (AUC=0.8738, p<0.0001) in sera from HB.The precision alteration of the XBPs referred to pathological changes in liver fibrosis/cirrhosis may provide pivotal information to discover the biomarkers for diagnosis of liver fibrosis/cirrhosis and development of new anti-fibrotic strategies.