Background and aims: TRIF is one of the main intracellular adaptor proteins required for TLR3 and 4 signaling. Abnormal gene expression of TRIF may lead to abrogated immune responses against viral infections including hepatitis B infection. The aim of this study was to identify the mRNA levels of TRIF in PBMCs isolated from chronic HBV (CHB) infected patients. Material and methods: mRNA was isolated from 63 CHB patients and 60 healthy controls and transcript levels of TRIF were examined in parallel with beta-actin (as housekeeping gene) using Real-Time PCR techniques. Results: Our results demonstrated that expression of TRIF was significantly decreased in PBMCs isolated from CHB patients when compared to healthy controls. Conclusions: Based on the results reported here, it seems that CHB patients are unable to express appropriate levels of the TRIF gene, which may attenuate TLR3 and 4 signaling subsequent to HBV infection. Our results suggest a possible mechanism, which may explain why hepatitis B infection is stable in CHB patients.