Here, we established a single-cell RNA-sequencing (scRNA-seq) dataset of HBV immune responses in patients to contribute to a better understanding of the dysregulated immune response in CHB. We collected blood samples of a well-defined cohort of CHB and healthy controls including a subset of matched blood and liver samples. scRNA-seq data of 55,825 total immune cells as well as 131,367 sorted HBV-specific, non-naive and PD1+ T cells was generated using the 10X Genomics platform (186,123 cells) and the full-length Smart-seq2 protocol (1,069 cells). This unique scRNA-seq dataset serves as a resource describing T cell responses in patients and offers the opportunity to explore transcriptional changes underlying HBV-related immune cell dysfunction in blood and liver tissue and to identify new targets or biomarkers for HBV-related immune exhaustion. This dataset incluces the 10X Genomics data only.