Background and Objectives: Vaspin is a novel adipocytokine. Various studies have shown that vaspin is associated with many types of cancer. This study aims to determine the association of vaspin rs2236242 gene polymorphism with vaspin level in women with papillary thyroid cancer (PTC) and Multinodular goiter (MNG). Methods: In this case-control study participants were 134 women. They were divided into three groups; PTC (n=49), MNG (n=30) and control (n=55). Ten milliliter peripheral blood samples were taken from participants, 5 ml was used for DNA extraction and 5 ml for preparation of serum. The vaspin level was measured by Sandwich ELISA kit. The genotype determination of vaspin rs2236242 polymorphism was done using the tetra primer-amplification refractory mutation system/polymerase chain reaction method. Results: There were no significant difference in serum vaspin level among the three groups. There was no significant association between genotypes of vaspin rs2236242 polymorphism and serum vaspin level in any groups. Logistic regression analysis showed that the difference in the frequency of the genotypes of rs2236242 polymorphism in the MNG group was significant compared to the control group. The TA genotype showed a protective effect against PTC and MNG (P<0.05). Conclusion: There is no significant difference in vaspin level between PTC, MNG and control groups. There is no association between rs2236242 gene polymorphism and serum vaspin level. The TA genotype of rs2236242 has a protective effect against MNG.