Recent research has associated the interferon-induced transmembrane protein 3 gene (IFITM3) with the outcomes of coronavirus disease 2019 (COVID-19), although the findings are contradictory. This study aimed to determine the relationship betweenIFITM3gene rs34481144 polymorphism and clinical parameters with COVID-19 mortality. The tetra-primer amplification refractory mutation system–polymerase chain reaction assay was used to analyzeIFITM3rs34481144 polymorphism in 1,149 deceased and 1,342 recovered patients. The clinical parameters were extracted from the patients' medical records. In this study, the frequency ofIFITM3rs34481144 CT genotypes (OR 1.47, 95% CI 1.23–1.76,P< 0.0001) in both sexes was significantly higher in deceased patients than in recovered patients. Moreover,IFITM3rs34481144 TT genotypes (OR 3.38, 95% CI 1.05–10.87,P< 0.0001) in women were significantly associated with COVID-19 mortality. The multivariable logistic regression model results indicated that mean age (P< 0.001), alkaline phosphatase (P= 0.005), alanine aminotransferase (P< 0.001), low-density lipoprotein (P< 0.001), high-density lipoprotein (P< 0.001), fasting blood glucose (P= 0.010), creatinine (P< 0.001), uric acid (P< 0.001), C-reactive protein (P= 0.004), 25-hydroxyvitamin D (P< 0.001), erythrocyte sedimentation rate (P< 0.001), and real-time PCR Ct values (P< 0.001) were linked with increased COVID-19 death rates. In conclusion,IFITM3rs34481144 gene polymorphism was linked to the mortality of COVID-19, with the rs34481144-T allele being especially important for mortality. Further studies are needed to confirm the results of this study.