Chronic lymphocytic leukemia (CLL) is a type of blood cancer that is characterized by the accumulation of abnormal lymphocytes in the bone marrow, lymph nodes, and other tissues. The prognosis of CLL varies widely, with some patients experiencing a relatively benign disease course while others progress rapidly to a more aggressive form of the disease. Recent research has identified several molecular pathways that may impact CLL prognosis, including many axes composed of messenger RNA (mRNA)for tumor suppressor pathways, long non-coding RNA (lncRNA), and microRNA (mRNA).Our study on 75 male and female B-CLL patients for p53, lincRNA-p21, and miR-34a biomarkers assessment for CLL prognosis. Our results showed that p53 and lincRNA-p21 increased with no significant difference between males and females. On the other hand, miR-34a expression decreased significantly compared to the control group. Results suggested that lincRNA-p21 and miR-34a may interact in a complex feedback loop that regulates p53 function and cellular processes in CLL. Dys-regulation of this feedback loop can contribute to CLL pathogenesis and may serve as a potential therapeutic target. Therefore, p53, lincRNA-p21, and miR-34a proved to be important molecular regulators of CLL pathogenesis and prognosis. Dys-regulation of these pathways can contribute to CLL progression and may serve as potential biomarkers or therapeutic targets. Further research is needed to better understand these pathways' complex interactions and develop more effective treatments for CLL patients.