Objective To investigate the analgesic effect of small dose ketamine, and its impact on the expression of plasma tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in patients after total hip replacement. Methods A total of 80 patients (with age of 65 to 80 and ASA grade Ⅰ to Ⅲ) after total hip replacement underwent patient controlled intravenous analgesia (PCIA) in our department. They were randomly divided into two groups: fentanyl and ondansetron group (F group, 20μg/kg fentanyl＋8mg ondansetron＋normal saline till 100ml, n＝40), and small dose ketamine combined with fentanyl and ondansetron group (KF group, 16μg/kg fentanyl＋2mg/kg ketamine＋8mg ondansetron＋normal saline till 100ml, n＝40) at a continuous intravenous infusion of 2ml/h. Visual analogue scale (VAS), mean aterial pressure (MAP), blood oxygen saturation (SpO2), side-effects during PCIA (such as nausea and vomiting), and the plasma levels of TNF-α and IL-1β were recorded and compared between the two groups at different time points. Results There was no significant difference in the VAS, sedation score, MAP and SpO2 between the two groups at all time points (P＞0.05), but the incidence of side-effects was significantly lower in KF group than in F group (P＜0.05). No significant difference was found in the plasma level of IL-1β between the two groups in 0 and 4h after operation; but in 12 and 24h after operation, that in KF group was significantly lower (P＜0.05). No significant difference was found in the level of TNF-α between the two groups at all time points. (P＞0.05). Conclusion Small dose ketamine combined with fentanyl in PCIA has better analgesic effect than conventional method of using fentanyl alone for patients after total hip replacement. It also reduces the incidence of nausea and vomiting and inhibits the expression of inflammatory factor IL-1β, and thus is helpful to patient’s recovery.