Context . Hepatitis B can develop into cirrhosis, and most liver cancers evolve on the basis of chronic hepatitis and cirrhosis. Manypatients are alreadyat an advanced stage when diagnosed. In recent years, clinicians have advocated detection of liver cancer using multiple markers in combination to improve the sensitivity and specificity of testing. Objective . The study aimed to evaluate the clinical value of using four tumor indicators-urea, alpha L-fucosidase (AFU), carbohydrate antigen 153 (CA153), carbohydrate antigen 125 (CA125), and alpha fetoprotein (AFP) and comparing the use of combined indicators to use of a single indicator for the diagnosis of liver cancer. Design . The research team performed a prospective study. Setting . The study took place at Clinical Laboratory, Baoding People's Hospital, Baoding City, Hebei Province, China. Participants . Participants were 98 patients with chronic hepatitis B, who became the CHB group; 102 patients with liver cirrhosis, who became the cirrhosis group, and 100 patients with liver cancer, who became the liver cancer group. They all had been admitted to the hospital between March 2019 and March 2021. Outcome Measures . The research team measured the urea, AFU, CA153, CA125, and AFP levels of the three groups, constructed an ROC curve, and analyzed the diagnostic values of the indicators singly and in combination for liver cancer. Results . For the levels of urea, AFU, CA153, CA125, and AFP, the CHB group's levels were significantly lower than those of the cirrhosis and liver cancer groups (both P <.001), and the cirrhosis group's levels were significantly lower than those of the liver cancer group (P <.001). In the CHB group, the compensatory group's levels were significantly lower than those of the decompensated group (P <.05). In the cirrhosis group, no significant differences existed between the levels of the grade A and grade B groups (P <.001), between those of the grade A and grade C groups (P <.001), or between those of the grade B and grade C groups (P <.001). In the cirrhosis group, the levels of the no ascites group were significantly lower than those of the ascites group (P <.05). In the liver cancer group, the levels of the stage I-II group were significantly lower than those of the stage III and stage IV groups (both P <.05), and those of the stage III group were significantly lower than those of the stage IV group (P <.05). The levels of the <5cm group were significantly lower than those of the =5cm group (P <.001). The value of using a combination of indicators for diagnosis was significantly higher than that of a single indicator (P <.001). Conclusions . Urea, AFU, CA153, CA125, and AFP all have diagnostic value in the evaluation of chronic hepatitis B-cirrhosis and liver cancer, with the highest efficacy, sensitivity and specificity from a combined test and diagnosis (Altern Ther Health Med. 2023;29(3):153-159).