Matrix metalloproteinase-12(MMP-12) is involved in tumor invasiveness and metastasis and significantly over-expressed in tissues of HCC. The Aim was to investigate the diagnostic and prognostic value of non-invasive MMP-12 expression in human HCC patients from whole blood.The study was conducted on; 50 patients with chronic HCV related HCC, 50 patients with HCV related cirrhosis and 50 healthy persons as a control group recruited from the National Liver institute, Menoufia University, Egypt. All patients were subjected to tri-phasic CT abdomen when indicated, liver profile, AFP and Molecular characterization of metalloproteinase-12 expression by (qRT-PCR) quantitative real time PCR. We found that, there was statistically significant differences between HCC and cirrhotic patients versus control group regarding CBC parameters and liver profile, (p- value < 0.01), while there was no differences between all groups regarding creatinin (p- value > 0.05). There was a statistically significant difference between HCC patients and other groups regarding mRNAMMP12 (p- value < 0.01). The Sensitivity of MMP12 to detect HCC cases was 72.0 %, and specificity 60.0 %, with accuracy 70.9 %, P value <0.01, mRNA-MMP12 and/or AFP had sensitivity of 84.0 %, specificity 60.0 %, PPV of 51.2%, NPP 88.2 % and Accuracy 71.3 %. In Conclusion: mRNA-MMP12 is a good sensitive, bad specific but accurate in diagnosing HCC. Adding mRNA-MMP12 to AFP improves early diagnosis and hence better prognosis.