Vaso-occlusion is the most signs and symptoms of sickle-cell anemia (SCA). Elevated Homocysteine concentration contributes to form thrombosis, a frequent event in sickle cell anemia. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme, which modifies homocysteine metabolism, and some polymorphisms of gene encoding this enzyme are accompanied with a decreased activity of the enzyme. The aim of the study was to study the association between the A1298C polymorphism and the incidence of Vaso-occlusive crisis. A case-control study was conducted over a period of one year from Jan-Dec 2014 inclusive, 50 patients were collected together with age, and sex matched healthy control 30 cases. Venous blood samples were collected from groups to estimate serum Homocysteine, folic acid and A1298C polymorphism identification through tetra primer ARMS PCR. Statistical analysis was done, using the student t-test, Pearson correlation analysis and χ2 test. We found that, the homocysteine level was significantly upregulated in the patients group compared with control group with p value > 0.01. Moreover, a strong positive correlation between Homocysteine level and the frequency of Vaso-occlusive crisis was found (χ2= 4.836 and p value 0.04). Association between vaso-occlusive events and polymorphism frequency showed a non-significant difference for the A1298C gene (χ2 = 1.720; p = 0.4231). We conclude that Hyperhomocysteinaemia is positively correlated with the frequency of Vaso-occlusive crisis and the presence of A1298C MTHFR gene polymorphism is not a risk factor for vaso-occlusive crisis in the SCD patients.