Background: Hepatocellular carcinoma (HCC) ranks among the top causes of cancer-related deaths globally. Astrocyte elevated gene 1 (AEG-1) plays a crucial role in cancer development and progression by enhancing all hallmarks of cancer. Glypican3 (GPC3) is a proteoglycan found on the cell surface and shows significant overexpression in hepatocellular carcinoma. This study aimed to assess the diagnostic utility of AEG1 and Glypican3 in HCC with their different grades and precancerous lesions. Material and methods: 60 cases were analyzed in this study, comprising 36 cases of HCC and 24 cases of precancerous lesions. The specimens underwent routine hematoxylin, eosin staining and immunohistochemical staining using AEG1 and GPC3 markers. Results: AEG1 was expressed in 94.4% of HCC cases and 12.5% of precancerous lesions, achieving a sensitivity of 94.4% and specificity of 87.5%. In comparison, GPC3 was expressed in 75% of HCC cases and 8.3% of precancerous lesions, with a sensitivity of 75% and specificity of 91.6%. GPC3 expression shows a statistically significant relation with high tumor grade, whereas AEG1 did not show a statistically significant relation with tumor grade. Combination of AEG1 and GPC3 demonstrated enhanced sensitivity (98.2%) and absolute specificity (100%), making the combined immunohistochemical panel highly effective for accurately diagnosing HCC and distinguishing it from precancerous lesions. Conclusion: AEG1 demonstrated higher sensitivity and diagnostic accuracy compared to GPC3, whereas GPC3 exhibited greater specificity. A combined immunohistochemical panel of AEG1 and GPC3 can be effectively utilized to achieve accurate diagnosis of HCC and to differentiate HCC from precancerous lesions.