Objective This paper aims to analyze and summarize the clinical and laboratory characteristics of patients with T-cell large granular lymphocytic leukemia (T-LGLL) and explore the diagnosis and treatment of T-LGLL. Methods A retrospective analysis was conducted on the clinical data of 6 T-LGLL patients treated at our hospital from March 2019 to December 2022. The cell morphology, bone marrow cell immunophenotyping, genetic testing results, and treatment plans were analyzed and summarized, with follow-up conducted. Results The median age at diagnosis of the 6 T-LGLL patients was 60 (range 54-70) years. All 6 patients presented with anemia at the time of consultation, with 3 requi-ring blood transfusion, 3 having splenomegaly, and 1 having lymphadenopathy. Peripheral blood LGL morphology was typical in all 6 cases, but with low absolute counts. The median count was 1.0 (range 0.4-1.4) × 10⁹/L. Bone marrow cell immunophenotyping showed that all patients’ LGL cells originated from post-thymic mature T cells. 4 patients expressed the common CD3⁺CD8⁺CD57⁺ effector T-cell markers, while 2 expressed the rare CD3⁺CD8⁺CD57^- memory T-cell markers. Genetic testing revealed monoclonal fragments in the T cell receptor (TCR) of all 6 patients, supporting the clonal abnormality. The next generation gene sequencing results showed STAT3 mutations in 4 of the 6 patients. All 6 patients received immunosuppressive therapy, and follow-up revealed that 5 patients responded to the treatment and 5 out of 6 patients achieved continuous hematological remission. Conclusions The diagnosis of T-LGLL cannot be accurately and early made solely based on typical cell morphology and absolute LGL counts. Additionally, there are significant variations in LGL immunophenotypes. Therefore, an integrated multi-parameter diagnostic approach combining morphology, immunophenotyping, TCR clonal analysis, and molecular biology data from next-generation sequencing is recommended. Currently, immunosuppressive therapy shows good treatment response.