Objective To explore treatment strategy of pancreatic pseudocyst induced left-sided portal hypertension (LSPH) complicated with hypersplenism. Methods The clinical data of 49 cases of pancreatic pseudocyst induced LSPH complicated with hypersplenism from January 2010 to June 2015 in this hospital were retrospectively analyzed. Among them, 36 patients who were not complicated with upper gastrointestinal bleeding were designed to splenectomy group and non-splenectomy group based on splenectomy or not. The epidemiological and clinical features, intraoperative and postoperative results of these two groups were compared. Results There were 38 males and 11 females with age ranging from 22 to 67 years old. As for 13 patients suffering LSPH complicated with hypersplenism caused by pancreatic pseudocyst with upper gastrointestinal bleeding, one patient didn’t accept splenectomy, then the upper gastrointestinal bleeding recurred and the hypersplenism was not alleviated after operation; Whereas, the hypersplenisms were relieved in the others patients after operation. In the 36 patients without upper gastrointestinal bleeding who were complicated with hypersplenism, 23 patients were performed splenectomy (splenectomy group) and 13 patients were not (non-splenectomy group). In the splenectomy group, the blood loss, operation time, and intraoperative blood transfusion were significantly more than those of the non-splenectomy group (P<0.05). The hospital stay and the discharged laboratory examinations had no significant differences between the splenectomy group and the non-splenectomy group (P>0.05) except for the platelet count. Furthermore, the incidence of the postoperative upper gastrointestinal bleeding was lower (P<0.05) and the relief rate of hypersplenism was higher (P<0.05) in the splenectomy group as compared with the non-splenectomy group. Conclusions For pancreatic pseudocyst induced LSPH with hypersplenism, we should be vigilant and early intervent. Usually, primary focus can be treated only. However, splenectomy can effectively relieve hypersplenism and prevent recurrent bleeding for patients with upper gastrointestinal bleeding or patients with close adhesion of pancreas tail and spleen inflammatory lesions and constricting splenic hilus.