Objective To investigate the expression characteristics and significance of function-related molecules of natural killer (NK) cells and natural killer T (NKT) cells in peripheral blood of patients with hepatitis B virus-related liver cirrhosis (HBV-LC). Methods Peripheral blood samples from 25 patients with compensated HBV-LC (HBV-CLC), 25 with decompensated HBV-LC (HBV-DLC) and 25 healthy controls (HC) in the same period were collected, and the proportion and quantity of NK and NKT cells in peripheral blood and the expression levels of activation markers such as CD69 and HLA-DR, activating receptors such as NKG2D, NKp30 and NKp46, inhibitory receptors such as NKG2A, CD158a and CD158b and cytotoxic molecules such as perforin, granzyme A/B, tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and IFN-γ of peripheral NK and NKT cells were detected by flow cytometry. Results Compared with HC and HBV-CLC patients, the proportion and quantity of NK cells in peripheral blood of HBV-DLC patients were significantly reduced (P＜0.01), while the expression levels of HLA-DR were increased obviously (P＜0.01). Compared with HC, the proportion and quantity of NKT cells in peripheral blood of HBV-DLC patients were significantly reduced (P＜0.05), while the expression levels of CD69 and HLA-DR were increased obviously (P＜0.05). In addition, the proportion of NKT cells in peripheral blood of HBV-CLC patients was significantly lower than that of HC (P＜0.05). However, there were no significant differences in the quantity of NKT cells and expression levels of activation markers between them (P＞0.05). There were no significant differences in the expression levels of inhibitory receptors (NKG2A, CD158a and CD158b) and most activating receptors such as NKp30 and NKp46 among the HBV-CLC, HBV-DLC and HC groups (P＞0.05). Compared with HC, the expression levels of NKG2D of NK cells in peripheral blood of HBV-LC patients were significantly reduced, while the expression levels of cytotoxic molecules such as perforin, granzyme A, TRAIL and IFN-γ of NKT cells in peripheral blood were significantly increased (P＜0.05). The expression levels of some cytotoxic molecules such as perforin and TRAIL of NK cells in peripheral blood of HBV-DLC patients were increased obviously (P＜0.05). Compared with HBV-CLC patients, the expression levels of perforin of NK cells in peripheral blood of HBV-DLC patients were reduced (P＜0.05), while the expression levels of NKG2D of NKT cells were increased and the quantity of NKT cells and the expression levels of IFN-γ were decreased (P＜0.05). Compared with HC and HBV-CLC patients, the killing ability of NK cells in peripheral blood of HBV-DLC patients was significantly inhibited (P＜0.01). Conclusion The function characteristics of NK and NKT cells in peripheral blood of HBV-LC patients, especially HBV-DLC patients, have been changed significantly, which may provide a new perspective and theoretical basis for the immune prevention and treatment of HBV-LC patients.