The single nucleotide polymorphism (SNP) ss469415590 in the interferon lambda-4 (IFNL4) gene has recentlybeen reported to have an association with treatment response in chronic hepatitis C. However, any importanceof the SNP in association with response to pegylated interferon (PEG-IFN) therapy in patients with chronichepatitis B (CHB) is unclear. We retrospectively analyzed data for Thai patients with CHB treated with PEGIFNfor 48 weeks. Virological response (VR) for HBeAg-positive CHB was defined as HBeAg seroconversion plusHBV DNA level <2,000 IU/mL at 24 weeks post-treatment. VR for HBeAg-negative CHB was defined as an HBVDNA level <2,000 IU/mL at 48 weeks. The SNP was identified by real time PCR using the TaqMan genotypingassay with MGB probes. A total 254 patients (107 HBeAg-positive and 147 HBeAg-negative) were enrolled inthe study. The distribution of TT/TT, ΔG/TT and ΔG/ΔG genotypes was 221 (87.0%), 32 (12.6%) and 1 (0.4%),respectively. Patients with non-TT/TT genotypes had significantly higher baseline HBV DNA levels than patientswith the TT/TT genotype. In HBeAg-positive CHB, 41.2% of patients with TT/TT genotype versus 50.0% withnon-TT/TT genotype achieved VR (P=0.593). In HBeAg-negative CHB, the corresponding figures were 40.3%and 43.5%, respectively (P=0.777). There was no significant correlation between the SNP genotypes and HBsAgclearance in both groups of patients. In summary, ss469415590 genotypes were not associated with response toPEG-IFN in Thai patients with HBeAg-positive and HBeAg-negative CHB.