Abstract: Objective To investigate the expression and significance of the inhibitory receptor T-cell immunoglobulin and ITIM domain (TIGIT) on peripheral blood natural killer (NK) cells in patients with myasthenia gravis (MG). Methods A total of 34 initially diagnosed MG patients, including 16 patients with generalized MG (GMG) and 18 patients with ocular MG (OMG), and 20 healthy controls at the Affiliated Hospital of Xuzhou Medical University and the People's Hospital of Jiangwa Distract of Xuzhou City were selected and their peripheral blood samples were collected. These 34 MG patients were evaluated by the Quantitative Myasthenia Gravis (QMG) scores. The NK cell subsets and surface markers (TIGIT, perforin and granzyme B), follicular helper T cells (Tfh cells) and their ligand CD155, and plasma cells were detected by flow cytometry. The acetylcholine receptor antibody (AChR-Ab) titer was measured by ELISA. The correlation between the proportion of TIGIT⁺ NK cells and Tfh cell ratio, plasma cell ratio, perforin and granzyme B levels, QMG score, and AChR-Ab titer was analyzed. Results Compared with the healthy controls, MG patients showed decreases in the proportion of CD3^-CD56⁺ NK cells in the peripheral blood (P<0.05, P<0.001), primarily in the CD56^dimCD16⁺ NK cell subset (P<0.05), with the GMG group showing a greater reduction than the OMG group (P<0.05). The proportion of CD56^brightCD16^- NK cells did not show a significant difference between MG patients and healthy controls (P>0.01). The levels of TIGIT on NK cells in the peripheral blood of MG patients were significantly higher than those in the healthy control group (P<0.001), with the GMG group showing a greater increase than the OMG group (P<0.01). The proportion of Tfh cells in MG patients increased, compared with those in healthy controls (P<0.001), with the GMG group having a higher proportion than the OMG group (P<0.05). The expression of the Tfh cell surface ligand CD155 in MG patients significantly increased, compared with those in healthy controls (P<0.001), with the GMG group showing higher expression than the OMG group (P<0.01). The secretion of perforin and granzyme B by NK cells in MG patients was lower than that in healthy controls (P<0.05), with the GMG group showing significantly lower levels than the OMG group (P<0.05). The proportion of plasma cells in the peripheral blood of MG patients was elevated compared with healthy controls (P<0.001), with the GMG group showing a more significant increase (P<0.001). The proportion of TIGIT⁺ NK cells was positively correlated with the Tfh cell ratio, QMG score, AChR-Ab titer, and plasma cell proportion (P<0.05), and negatively correlated with granzyme B and perforin levels (P<0.05). Conclusions The expression of TIGIT on NK cells is abnormal in MG patients and correlated with the secretion of perforin and granzyme B by NK cells and the severity of the disease.