Background: The α and β adrenoblockers have been tested as an alternative treatment for chronic liver lesions such as fibrosis and cirrhosis in animal models, as well as their possible participation during the regeneration of the damage caused by liver cirrhosis in a hamster model. However, it was observed that doxazosin caused slight morphological changes in hepatocytes, while that curcumin showed protection to the hepatic parenchyma. Regardless, the pharmacokinetic effects of these 𝛼/𝛽 adrenoblockers on the hepatocytes' cell viability, possibly involved in the hepatic parenchyma's repopulation during cirrhosis reversal, are unknown. The present study aimed to elucidate the protective effect of curcumin on the possible side effects of doxazosin, tamsulosin, and carvedilol on the HepG2 cell line, drugs already tested with antifibrotic activity.Methods: HepG2 cells were exposed to 0.1, 0.5, 10, and 25 µM of doxazosin, carvedilol, and tamsulosin for 24, 48, and 72 h, for curcumin, cells were pretreated with 1 µM for 1 h before exposure to α and β adrenoblockers. The cell viability was assessed by MTT assay. The morphological changes were determined using hematoxylin and eosin (H&E) staining, scanning electron microscope (SEM), and acridine orange (AO) staining. Results: We observed that the doxazosin decreases cell viability dependently time and dose; carvedilol and tamsulosin increase cell proliferation. However, curcumin induces regulation of these effects in HepG2 cell line, increasing or maintaining viability compared to control. The pretreatment with curcumin regulated AST levels (aspartate aminotransferase) and ALT (alanine aminotransferase) in cells exposed to α and β adrenoblockers. The SEM and H&E staining provided evidence that doxazosin, carvedilol, and tamsulosin induced morphological changes in HepG2 cell line, depending on time and dose, approximately 80% of the cells treated with drugs were balonized, and curcumin protected these effects, maintaining the morphology in 90% of the treated cells.Conclusions: The present study demonstrates that curcumin protected the HepG2 cells against cytotoxicity and morphological changes induced by the α and β adrenoblockers attenuating secondary effects for possible oxidative stress. In this way, it is concluded that these treatments with antifibrotic effect, in co-treatment with curcumin, will not affect the possible repopulation process of the liver parenchyma during the reversion of fibrosis.