Background: Systemic inflammation is a common host reaction to cancer progression. Serum level of buttyrylcholinesterase (BChE) have been reported to reflect the presence of inflammation and other clinical conditions. BChE is an alphaglycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, injury, infection, and malignant disease. We retrospectively evaluated the potential prognostic significance of buttyrylcholinesterase before chemotherapy as an independent predictor of overall survival in patients with advanced upper-tract urothelial cancer. Methods: We treated seventy-four patients (52 men and 22 women) with advanced upper-tract urothelial cancer (UTUC) at our clinic between August 2004 and September 2017. The average age was 69.3 (43–89), and average eGFR was 50.5 (11.6–99.3) ml/minute/1.73m². Mean observation period was 28.7 (3–111) months. Levels of serum BChE (normal range 168-470 U/L) were measured 1 week before chemotherapy. The average serum level of BChE were 240.6 U/L (53-509). The patients received 2 courses of GCarbo consisted of 800mg/m² gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCcarbo was performed. If this regimen did not induce any tumor size reduction, we switched to 2 courses of GCarboD (D; 70mg/m²) treatment as second-line treatment. Results: GCarbo regimen yielded 5 cases (6.8%) of CR, 32 (43.2%) of PR, and the average duration of response of 11.4 (2–29) months. GCarboD treatment was administered in 21 cases, and yielded 2 (9.5%) PR and a duration of response was 31.5(7-50) months. The median over-all survival period was 14.3 months. When analyzed by serum BChE level, the ovearall survival were 22.0 months in the BChE > 168 U/L group and 11.0 months in the BChE < 168 group (p = 0.0035). The level of serum BChE showed no association with treatment effect. Conclusions: Serum BChE level before chemotherapy may have the potential to predict overall survival in patients with advanced upper-tract urothelial cancer.