Systematic reviews on osteosarcoma have concluded that CTLA4 rs231775 AA genotype influences risk for the disease in the Chinese population. Remarkably, rs231775 shows different frequencies in different human populations. Therefore, it would be interesting to know whether this SNP is related to the risk of osteosarcoma in other populations. The present study aimed to evaluate the association between rs231775 and the susceptibility of osteosarcoma in the Spanish population. We performed an updated meta-analysis including a total of 538 cases and 623 controls. The genotypic association analyses showed that the CTLA4 rs231755 was associated with osteosarcoma susceptibility in the Spanish population. When meta-analysis was performed, the results displayed that CTLA4 rs231775 AA genotype was associated with the risk of developing osteosarcoma in all analyzed populations (OR=2.07; 95% CI: 1.48-2.89).The rs231775 AA genotype could be considered as a susceptibility marker in osteosarcoma Keywords: CTLA4, rs231775, +49A/G and osteogenic sarcoma.