BackgroundTo apply non-invasive Automatic Tongue Diagnosis System (ATDS) in analyzing tongue features in patients with chronic kidney disease (CKD). MethodsThis was a cross-sectional, case-controlled observational study. Patients with CKD who met the inclusion and exclusion criteria were enrolled and divided into the following groups according to renal function and dialysis status: non-dialysis CKD group; end-stage renal disease (ESRD) group; and control group. Tongue images were captured and eight tongue features—shape, color, fur thickness, saliva, fissure, ecchymosis, teeth marks, and red dots—were imaged and analyzed by ATDS. Results117 participants (57 men, 60 women) were enrolled in the study, which included 16 in control group, 38 in non-dialysis CKD group, and 63 in ESRD group. We demonstrated significant differences in the fur thickness (p = 0.045), color (p = 0.005), amounts of ecchymosis (p = 0.010), teeth marks (p = 0.016), and red dot (p < 0.001) among three groups. The areas under receiver operating characteristic curve for the amount of ecchymosis was 0.757 ± 0.055 (95% confidence interval, 0.648–0866; p < 0.001). Additionally, with increase in ecchymosis by one point, the risk of CKD dialysis rose by 1.523 times (95% confidence interval, 1.198–1.936; p = 0.001). After hemodialysis, the amount of saliva (p = 0.038), the area of saliva (p = 0.048) and the number of red dots (p = 0.040) were decreased significantly among patients with ESRD. On the contrary, the percentage of coating (p = 0.002) and area of coating (p = 0.026) were increased significantly after hemodialysis. ConclusionBlood deficiency and stasis with qi deficiency or blood heat syndrome (Zheng pattern) is common in patients with CKD. The risk of CKD dialysis increases with increasing ecchymosis. Hemodialysis can affect saliva, tongue coating, and relieve heat syndrome among ESRD patients.