Hepatitis C virus (HCV) is endemic in Egypt. Over 15% of populations of the people in Egypt are infected, this is ten times greater than in any other country in the world. To validate a simple, inexpensive, non invasive markers (Fib-4, APRI, syndecan-1 and apolipoprotein A-1(ApoA-1) for detection of liver fibrosis in patients with chronic HCV and thereby reduce the need for liver biopsy. Estimation of serum syndecan-1 and apoA-1 by ELISA were done on 20 normal healthy persons and 57 chronic hepatitis C patients, the patients were staged according to liver biopsies (Metavir fibrosis staging) (stage f1=15, f2=15, f3=14,f4= 13). The area under the receiver operating characteristic (ROC) curve (AUC) of syndecan-1=(0.72), the mean level of plasma syndecan-1 was significantly higher in chronic HCV patients when compared to control subjects (P=0.0008), but the mean level of ApoA-1 was not significantly different from that of controls (p=o.65), and it had significant negative correlation to the stage of fibrosis (AUC=0.57). Moreover the APRI and Fib-4 were proved significantly directly correlated with fibrosis stage of the studied patients. This study not reveals putative biomarkers of liver fibrosis (syndecan-1, ApoA-1 APRI, Fib-4) but also proves the differential expression of those markers in different stages of fibrosis. It is expected that combination of these novel biomarkers could be applied clinically to predict the stage of liver fibrosis without the need of liver biopsy.