Introduction: The thymus slowly involutes with age after puberty. Various stress conditions accelerate the involution of the thymus and cause changes in the histologic structure of the gland. Objective: The present study performed histomorphological and immunohistochemical (IHC) evaluations of the thymus glands removed during surgical repair in patients with cyanotic or acyanotic congenital heart disease (CHD). The thymus glands in the hypoxic group were compared to those in the non-hypoxic group. This study suggested that the activation of HIF-1 alpha promotes tumor progression and impair prognosis due to the inhibition of apoptosis, increased population of stem cells, and induction of angiogenesis also suggested that inactivation of HIF-1 alpha in tumor-infiltrated tissues could halt tumor progression and improve prognosis. Materials and methods: The study included 76 thymus glands removed from patients who underwent an operation due to CHD. Of these cases, 38 had cyanotic CHD, and constituted the hypoxic group. The remaining 38 patients had acyanotic CHD, and constituted the non-hypoxic group. IHC procedures were performed for HIF-1 alpha, FoxP3, CD44, Bcl-2, and CD34. Results: There were statistically significant differences between the hypoxic and non-hypoxic groups only in terms of medullary enlargement toward the cortex and effacement of the corticomedullary junction. In the immunohistochemical examination for five markers, staining intensity and staining rates increased with decreasing oxygen saturation. Conclusion: It can be concluded that the activation of HIF-1 alpha promotes tumor progression and impair prognosis due to the inhibition of apoptosis, increased population of stem cells, and induction of angiogenesis.