Objectives: To explore the clinical value of contrast-enhanced computed tomography (CECT) combined with contrast-enhanced ultrasound (CEUS) for characterization and diagnosis of small nodular lesions in the liver and investigate the association between such small nodular lesions and the degree of tumor differentiation. Methods: Combined imaging modalities were performed on 120 patients who were admitted by Linyi Maternal and Child Health hospital from December 2018 to December 2020 and diagnosed with hepatic nodular lesions. The CT scans were interpreted by two senior imageologists while the ultrasound scans were analyzed by two senior sonographers. A comparative analysis was carried out on different scan modes and the postoperative or post-puncture pathological results using the t-test, the χ2 test, and the Pearson’s correlation analysis. Results: Compared to the pathological results, definite diagnoses of 55 malignant cases were made using CECT alone, with the coincidence rate of 78.6%; CECT combined with CEUS formed correct diagnoses in 64 cases, and the coincidence rate was up to 91.4%. The difference between the two scan modes was statistically significant (p= 0.03). Based on pathological diagnosis, seventy out of the 120 cases of small nodular lesions were identified as malignant, while the other 50 cases were benign. The single imaging modality diagnosed 63 malignant and 57 benign nodules, whereas the combined modalities identified 68 malignancies and 52 benign conditions. Compared to CECT as a single imaging modality, the combined modalities showed a higher degree of sensitivity and accuracy, and the difference was statistically significant (sensitivity: p= 0.03; accuracy: p= 0.02); in the malignant cases, the magnitudes of contrast enhancement of CT and ultrasound imaging decreased with an increase in the degree of differentiation, indicating a negative correlation between these factors. Conclusions: CECT combined with CEUS has a higher coincidence rate, greater sensitivity, and better diagnostic accuracy when being used for characterization and diagnosis of small nodular lesions in the liver. A higher degree of tumor differentiation means a decreased magnitude of contrast enhancement and a blurrier boundary, which indicates that CECT and CEUS are complementary to each other in classifying malignant liver nodules. The use of the combined imaging modalities shows clinical value for characterizing small liver nodules and predicting the degree of malignancy. doi: https://doi.org/10.12669/pjms.37.7.4306 How to cite this:Liu J, Bao D, Xu Z, Zhuge X. Clinical value of contrast-enhanced computed tomography (CECT) combined with contrast-enhanced ultrasound (CEUS) for characterization and diagnosis of small nodular lesions in liver. Pak J Med Sci. 2021;37(7):---------.  doi: https://doi.org/10.12669/pjms.37.7.4306 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.