The diagnostic role of serum cytokines depends on the etiology and pathogenesis of acute appendicitis but the clinical significance of these cytokines in the differential diagnosis of complicated acute appendicitis remains unclear. To investigate the prediction of progression and diagnostic values of interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha in complicated acute appendicitis. This study was conducted in 100 patients with a definitive diagnosis of acute appendicitis and 20 individuals assigned for the control group. Venous blood was collected to assess biochemical tests, as well as interleukin-6, interleukin-1β, and tumor necrosis factor-α levels. Serum levels of all parameters were dramatically higher in the complicated group compared with uncomplicated. Duration of hospitalization, rates of postoperative infection, intraabdominal abscess, and re-hospitalization were higher in complicated group. Cut-off points of WBC, CRP, NLR, interleukin-6, interleukin-1β and tumor necrosis factor-α were 13.5x103/µL, 1.92 mg/dL, 6.09, 23.4 pg/mL, 5.6 pg/mL and 24 pg/mL (p=0.0014, p<0.001, p=0.009, respectively and p<0.001 for the rest). AUC of interleukin-6 was larger than AUCs of all other parameters, suggesting the highest predicting power of interleukin-6 among other parameters. Serum interleukin-6, interleukin-1β, and tumor necrosis factor-α levels are valuable diagnostic parameters to predict a complicated acute appendicitis.