BACKGROUND This study aimed to compare the application value of intraoperative fluorescence navigation technology (FNT) and intraoperative ultrasound (IOUS) in primary liver cancer surgery. MATERIAL AND METHODS Fifty consecutive patients with primary liver cancer scheduled to receive surgical treatment were divided into FNT group and IOUS group. FNT and IOUS were separately used to guide tumor resection and detect new cancerous lesions in the 2 groups. The complete tumor resection rate (R0) resection rate, length of the tumor distance from cutting edge, the diagnostic efficacy of cancerous nodules and the fluorescence imaging characteristics of different types tumors were recorded. RESULTS The R0 resection rate was 100% (25 out of 25 patients) in the FNT group and 96% (24 out of 25 patients) in the IOUS group. In the FNT group, 1 case (4%, 1 out of 25 patients) had cancer tissue that was less than 1 cm from the cutting edge, compared to 7 cases (28%, 7 out of 25 patients) in the IOUS group (P=0.049), which was a significant difference. In the remaining livers of 50 consecutive patients, FNT found 5 new cancerous nodules with a sensitivity of 71.4%, a specificity of 11.1%, and a false-positive rate of 88.9%; for IOUS the results were 42.9%, 88.9%, 11.1%. The fluorescence imaging characteristics of all well-differentiated hepatocellular carcinomas were tumor tissue imaging, but all other types of tumors were ring imaging around the tumor. CONCLUSIONS FNT can improve the R0 resection rate, ensure a safe distance between tumor and cutting edge and can identify more new cancerous nodules compared to IOUS. Thus, FNT could improve the surgical treatment effect for primary liver cancer and hopefully further improve the prognosis of patients.