Background: Beta-thalassemia major is a hereditary blood disorder characterized by severe anemia requiring lifelong regular blood transfusions. Repeated transfusions may lead to iron overload, which can cause oxidative stress, hepatocellular injury, and chronic inflammation. Serum glutamic-pyruvic transaminase (SGPT) and serum glutamic-oxaloacetic transaminase (SGOT) are commonly used to assess hepatocellular injury, whereas high-sensitivity C-reactive protein (hs-CRP) can detect low-grade systemic inflammation. Purpose: To determine the correlation between SGPT and SGOT levels and hs-CRP levels in pediatric patients with beta-thalassemia major. Method: This analytical observational study used a cross-sectional design and secondary data from medical records of pediatric patients with beta-thalassemia major treated at Pringsewu Regional General Hospital. Data were collected in February 2025 from records of patients treated between September and November 2024. A purposive sampling technique was used based on predetermined inclusion and exclusion criteria, resulting in 43 eligible patients. Data were analyzed using the Spearman correlation test with a significance level of p < 0.05. Results: The mean SGPT, SGOT, and hs-CRP levels were 58.86 ± 30.749 U/L, 55.67 ± 23.551 U/L, and 1.1216 ± 1.19167 mg/L, respectively. A significant positive correlation was found between SGPT and hs-CRP levels (p = 0.025; r = 0.341), indicating a weak positive correlation. A significant positive correlation was also found between SGOT and hs-CRP levels (p = 0.005; r = 0.421), indicating a moderate positive correlation. Conclusion: SGPT and SGOT levels were significantly and positively correlated with hs-CRP levels in pediatric patients with beta-thalassemia major. These findings suggest that hepatocellular injury and systemic inflammation may occur concurrently in patients with transfusion-dependent beta-thalassemia.