The p53 is a major gene involved in the determination of proliferation or growth arrest at the cellular level. This study aimed to examine the association of P53 codon 72 Arg/Pro polymorphism with Essential thrombocythemia. This study is a case control study conducted in Khartoum state. Three milliliter (ml) of venous blood was collected from 43 patients with essential thrombocythaemia and 30 healthy volunteers as a control group, DNA was extracted by salting out method, and target DNA regions of the P53 gene were amplified using allele specific polymerase chain reaction (PCR).The result showed that, Arg\ Arg (51%) genotype was the most common among patients with essential thrombocythemia, followed by pro/pro (33%) and Arg/pro (16%) genotypes consequently. In control group, the genotype Arg\Arg (80%) was the most frequent, followed by Arg\pro (17%) and pro\pro (3%)also consequently. A significant association was found between Arg/Arg genotype and ET (OR: 3.8, 95%CI: 1.302-11.1999, P. value: 0.015) Arg allele frequencies were 0.67 in patient’s subject, 0.80 in control while Pro allele frequencies were 0.33 in patient’s subject, 0.20 in control group. There was no statistically difference in mean platelet count according to genotype (p.value:0.799) P53 codon 72 Arg/Pro polymorphism is associated with the risk of essential thrombocythemia among Sudanese population. The polymorphism has no effect on platelet count.