The aim of the present study was to investigate the clinical efficacy of phased joint intervention [percutaneous transhepatic variceal embolization (PTVE) + phased partial splenic embolization (PSE)] in patients with portal hypertension complicated by esophageal variceal bleeding and hypersplenism and the effect of this intervention on interleukin-35 (IL-35)/IL-17 expression. A review of 53 patients with portal hypertension caused by liver cirrhosis and complicated by esophageal variceal bleeding and hypersplenism treated with phased joint intervention was conducted, and portal hemodynamics, routine blood examinations and liver function were determined. Quantitative polymerase chain reaction (qPCR) was used to evaluate EBI3, FOXP3 and IL-17 mRNA expression levels in peripheral blood mononuclear cells (PBMC) before and after the phased joint intervention, while western blot analysis was used to determine their protein expression. All 53 patients required emergency hemostasis resulting in an emergency hemostatic rate of 100%. Varicose veins disappeared, portal hemodynamics and liver function improved subsequent to the intervention. The expression levels of EBI3, FOXP3 and IL-17 mRNA in the postoperative group were significantly lower than the preoperative levels (P<0.01). The protein expression levels of EBI3, FOXP3 and IL-17 in the postoperative group were reduced compared with the preoperative levels. The concentrations of IL-35, IL-6 and IL-17 in peripheral blood were significantly reduced after the phased joint intervention (P<0.01). Serum IL-35, IL-6 and IL-17 levels were positively correlated with total bilirubin and international normalized ratio, and negatively correlated with albumin. The phased joint intervention can effectively treat esophageal variceal bleeding and hypersplenism, and improve liver function. The efficacy of this intervention may be associated with the regulation of immune function.