Hairy Cell Leukemia (HCL) is a rare disorder characterized by splenomegaly, pancytopenia and proliferation with ‘hairy’ lymphocytes. Treatment is based on purine analogs and anti-CD20 antibodies, often resulting in significant adverse effects. This study analyzed 20 patients treated between 2009 and 2023, focusing on clinical characteristics, treatment response, complications and survival outcomes. Cladribine treatment achieved complete response in 77.8% of patients. The 5-year OS and PFS were 100% and 91.7%, respectively. Infections, pathogens such as herpes viruses and mycobacteria, were major complications, impacting 38% of patients. Severe skin reactions were noted in patients treated with cladribine. The study highlights cladribine’s effectiveness in inducing remission in HCL patients, pointing out the significant risk of infections and other adverse effects. Introducing targeted treatments like BRAF inhibitors provides promising alternatives, especially for resistant patients or those intolerant to purine analogs. Future strategies should focus on integrating targeted therapies to reduce treatment-related morbidity.