Background: miRNA-122 has been reported to be a useful tool for monitoring ACR after LT. IL-28B SNP rs8099917 genotype is known to contribute to the control of HCV infection. We sought to investigate the relationship between IL-28B SNP rs8099917 genotype and miRNA-122 expression and immune mechanism of ACR after LT using hepatitis C antibody calibration. Patients and Methods: A total of 45 patients with chronic hepatitis C received LDLT. IL-28B SNP rs8099917 genotyping was used to divide TT and GT groups. The relative expression levels of miRNA-122 were calculated by quantitative PCR as 2[(Ct of miR-122) (Ct of U6)] normalized to a reference gene and compared to a control sample, and the anti-HCV titers before and after LT were tracked to observe the relationship with ACR. Results: In the genotype of rs8099917, TT was significantly more associated with higher serum miRNA-122 levels than GT (p = 0.029). The ACR was significantly higher in genotype TT than in GT (p = 0.002). TT was significantly associated with low levels of pre-LT anti-HCV compared with GT (p = 0.022). Multivariate analysis with 95% confidence intervals showed a significant association between rs8099917 genotype TT, lower pre-LT and higher post-LT anti-HCV and ACR. Conclusion: Based on our current data, IL-28B SNP rs8099917 genotype TT may express higher miRNA-122 and correlate with lower Pre-LT and higher Post-LT anti-HCV titers, and may correlate to the pathogenesis of ACR after LT.