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Toll like receptor 4 (TLR4) is an extracellular pathogen recognition receptor (PRR) which recognizes a wide range of pathogens and damage associated molecular patterns (PAMPs and DAMPs). It can activate intracellular signaling and consequently transcription factors which participate in transcription from either immune related or malignancy genes. Thus, it has been hypothesized that TLR4 may be a cause of hepatocellular carcinoma (HCC). This article has reviewed the roles of TLR4 in the pathogenesis of HCC.“TLR4”, “hepatocellular carcinoma”, “liver tumor” and “liver cancer” were used as key words for searching in Scopus, Google Scholar and MEDLINE scientific databases.Most of the investigations documented the roles of TLR4 in induction of HCC via several mechanisms including increased number of T regulatory lymphocytes and liver resident follicular helper like cells, increased production of pro-inflammatory and malignancy related molecules including cytokines, NANOG, Caspase-1, Ephrin-A1, NO and BCL6. TLR4 participates in the proliferation of the cells and also production of the molecules in both chronic infectious and non-infectious inflammatory diseases.TLR4 is an innate immunity receptor which plays a pathogenic role during chronic inflammation and can induce HCC in human.