Objective To investigate roles of nuclear factor-κB/myeloid differentiation factor 88 (NF-κB/MyD88) in the liver fibrosis of patients with cystic echinococcosis (CE). Methods Liver samples were collected from the liver lesion tissue surgically resected from CE patients, by taking the tissue proximal to the lesion (0.5 cm to the outer cyst wall) and distant normal tissue (2 cm to outer cyst wall). Pathological changes of liver samples were observed by HE staining. Collagen deposition was observed with Masson staining. Expression of hepatic stellate cell activation marker α-smooth muscle actin (α-SMA), NF-κB p65 and MyD88 in the liver tissues of CE patients was detected by immunohistochemical staining and qRT-PCR analysis. Pearson correlation coefficient method was used to analyze the correlation of the expression level of NF-κB p65 and MyD88 with the positive area of collagen deposition, and expression level of α-SMA. Results Forty liver lesion samples resected from CE patients were collected, among them there were eight CE1, ten CE2, seven CE3, nine CE4 and six CE5. Of the patients receiving surgery, 24 were males and 16 females, aged from 20 to 45 years with the median of (38.2 ± 12.9) year. HE staining showed that inflammatory microenvironment was formed between CE lesion and proximal liver tissue, presenting massive lymphocyte infiltration, accompanied by increase of granulocyte to different degree. Masson staining showed that collagen was mainly deposited in the inflammatory cell band in the tissue proximal to lesion, around portal areas, biliary ducts and blood vessels. The positive area of collagen deposition in proximal-lesion tissue (20.29 ± 3.96)% was higher than that (2.87 ± 1.74)% in distant normal liver tissue (t = 13.640, P < 0.01). Immunohistochemical staining demonstrated that α-SMA, NF-κB p65 and MyD88 positive cells mainly highly expressed in the inflammatory cell band around proximal-lesion tissue, which was (13.47 ± 3.47)%, (7.30 ± 1.40)% and (7.47 ± 1.86)%, respectively. However, their expression in distant normal liver tissue was quite low, which was (3.43 ± 0.56)%, (1.08 ± 0.29)%, (0.36 ± 0.05)%, respectively, showing significant difference of expression in proximal and distant location(t = 5.682, 18.530, 5.087, P < 0.01). qRT-PCR analysis indicated that relative expression amount of α-SMA, NF-κB p65, MyD88 mRNA in proximal-lesion samples was 5.05 ± 0.42, 3.71 ± 0.33, 7.11 ± 0.50, respectively, which was significantly higher than those in the distant normal tissues (1.07 ± 0.01, 1.02 ± 0.03, 1.07 ± 0.02, respectively) (t = 39.750, 34.130, 50.960, P < 0.01). The expression of NF-κB p65 and MyD88 was significantly correlated with the and positive area of collagen deposition and α-SMA expression (r = 0.98, 0.97, 0.98, P < 0.01). Conclusion NF-κB p65/MyD88 expression in the proximal-lesion liver tissue of hepatic CE patients was significantly higher than that in the distant normal liver tissue, which was positively correlated with the degree of liver fibrosis.