AbstractToll‐like receptors (TLRs) are components of innate immunity, but also have a role in carcinogenesis. The prognostic value of TLR5 and TLR8 tumor expression was examined in contrast with known risk markers Ki67 and p53. All HCC patients from Oulu University Hospital with available representative tumor sample were included in this study (n = 182). TLR5, TLR8, Ki67, and p53 expression were investigated by immunohistochemistry. The relation between patient survival and TLR, Ki67, and p53 expression was calculated with Cox regression adjusted for confounding factors. TLR5 cytoplasm intensity was associated with 5‐year overall (strong 0.0% vs weak 23.4%, p < 0.001) and disease‐specific (strong 0.0% vs weak 34.9%, p < 0.001) survival. TLR5 nuclei percentage was associated with poor 5‐year disease‐specific survival (high 16.3% vs low 31.5%, p = 0.022). In adjusted analysis, strong TLR5 cytoplasm intensity was an independent risk factor for poor 5‐year overall (adjusted HR 1.88, 95% CI 1.26–2.81) and disease‐specific (adjusted HR 2.00, 95% CI 1.27–3.15) survival. High Ki67 and p53 expression associated with 5‐year overall‐ and disease‐specific survival. TLR8 was not associated with patient survival. This study suggests that TLR5 expression is independently prognostic in HCC with similar point estimate as previously known p53.