This study aims to investigate the effects of controlled low central venous pressure combined with dexmedetomidine on the blood loss, renal function and cognitive function in patients undergoing laparoscopic hepatectomy. From January 2021 to October 2022, 90 patients treated with laparoscopic hepatectomy in Huai’an First People’s Hospital were selected as subject objects and equally divided into the study group and control group in a random method. The blood loss, surgical duration, duration of hepatic portal occlusion, serum bilirubin, creatinine, urea nitrogen, hemoglobin, plasma albumin, interleukin (IL)-6 and cognitive function in the two groups were compared. Patients in the study group receiving the combination of controlled low central venous pressure and dexmedetomidine showed less blood loss and shorter time of hepatic portal occlusion as compared to the control group. The levels of serum bilirubin, creatinine and urea nitrogen were significantly increased at postoperative 3 days compared with preoperation in the study and control groups. In particular, these factors were higher in control group than that in the control group at postoperative 3 days, indicating better liver function and renal function of patients in the study group than those in the control group. The levels of hemoglobin and plasma albumin observed in study group 3 days after surgery were higher than those in the control group. At 1 day after surgery, the level of IL-6 was significantly lower in the study group than that in the control group. Patients in the study group achieved significantly higher mini-mental state examination (MMES) scores than those in the control group at postoperative 1 day, 3 days and 7 days. The controlled low central venous pressure combined with dexmedetomidine is a promising clinical practice in decreasing blood loss, improving the liver and kidney function, and protecting the cognitive function of patients during laparoscopic hepatectomy.