Introduction: Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a novel transformation suppressor gene against ras oncogenes. It encodes a membrane-anchored glycoprotein that can negatively regulate matrix metalloproteinases (MMPs) and inhibit tumor invasion, angiogenesis and metastasis. Aim of work: The aim of this study was to analyze the association between RECK gene rs11788747 Single-nucleotide polymorphism (SNP) and HCC susceptibility and its association with various clinical and laboratory data of the patients. Subjects and methods: This study included 50 HCC patients (43 males and 7 females) and 50 age and sex matched healthy controls for comparison. All patients were subjected to history taking, physical examination, laboratory investigations, abdominal ultrasonography (US) and triphasic helical CT and/or dynamic MRI as well as analysis of RECK gene rs11788747 SNP using PCR-RFLP, which was done for both patients and healthy controls. Results: RECK rs11788747 A/G and G/G genotypes frequencies were significantly higher in HCC patients compared to the healthy controls. There has been a statistically significant relationship between schistosomiasis and RECK gene rs11788747 in HCC patients. The HCC patients possessing at least one mutant G allele were significantly at a higher risk of developing lymph node and distant metastasis. Serum alpha fetoprotein (AFP) level was a significant prognostic indicator among HCC patients carrying A/G or G/G genotypes. Conclusion: RECK rs11788747 polymorphism might be a risk factor increasing HCC susceptibility as well as lymph node and distant metastasis. However, RECK rs11788747 polymorphism may be linked to decreased prevalence of schistosomiasis among HCC patients carrying A/G or G/G genotypes.