AIM: To assess the value of gemstone spectral imaging (GSI) in efficacy evaluation in hepatocellular cancer (HCC) after transcatheter arterial chemoembolization (TACE) treatment. METHODS: Thirty patients with HCC underwent GSI, including nonenhanced, arterial, portalvenous and delayed phase scans, after TACE treatment. Arterial phase images were acquired with GSI for reconstruction of virtual nonenhanced images and color overlay images. Digital subtraction angiography (DSA) was performed in all these patients. Two blinded and independent readers evaluated the data in two reading sessions; standard nonenhanced, arterial, portalvenous, and delayed phase images were read in session A, and the optimal monochromatic images, iodine/water based images and spectrum features were read in session B. Sensitivity and specificity were calculated with the DSA data as the reference standard. The sensitivity and specificity were compared using the χ (2) test. RESULTS: DSA revealed 154 lesions in 30 patients, and 100 of them had blood supply. Overall sensitivity and specificity were 72% (72/100) and 77.8% (42/54) for session A, and 97% (97/100) and 94.4% (51/54) for session B, respectively. The sensitivity and specificity of the two reading sessions were significantly different (χ (2) = 23.04, χ (2) = 7.11, P < 0.05). CONCLUSION: Compared with conventional CT, GSI could significantly improve the detection of small and multiple lesions without increasing the radiation dose. Based on spectrum features, GSI could assess tumor homogeneity and more accurately identify residual tumors and recurrent or metastatic lesions during efficacy evaluation and follow-up in HCC after TACE treatment.