Hepatocellular carcinoma (HCC) was reported to have down-regulated DiGeorge syndrome critical region (5) (DGCR5). In HCC, it may function as a tumor-suppressive gene. To study DGCR5 relative expression level in HCC, a hundred and sixty participants were involved in this study. They were split up into two categories: Group I consisted of 70 patients with HCC identified by imaging (dynamic MRI or triphasic CT) or biopsy; Group II consisted of 90 healthy individuals acting as the control group. A complete history, a general clinical examination, the analysis of clinic pathological data for patients with HCC, and laboratory investigations were performed on all patients and controls. These procedures included the following: 1- Liver function tests, such as alpha-fetoprotein (AFP), aspartate and alanine transaminases (AST and ALT), total bilirubin and serum albumin, detection of HBsAg and HCV Ab. 2- Serum Creatinine. 3- Using real-time PCR, quantify the relative expression levels of (DGCR5). Serum creatinine, albumin, ALT, AST, and AFP levels were considerably higher in HCC patients than in controls, and DGCR5 relative expression level was down regulated. With total bilirubin, serum albumin, AST, and AFP, there was a statistically significant decline in the relative expression level of DGCR5 with TNM staging. Conclusion: DGCR5 acts as a tumor suppressor gene in HCC