Hepatocellular carcinoma (HCC) is a global health challenge with a predicted high mortality rate in the future. Thus, discovering novel natural metabolites trimming the progression of HCC is an urgent necessity. In this study, we aimed to evaluate the effect of cytotoxic alkaloids isolated from endophytic fungus Aspergillus fumigatus, extracted from Albizia lucidior leaves (Fabaceae), against Huh7 cells and to further reveal their possible mechanisms on TP53 and c-Myc and their downstream tumor suppressor microRNAs (miRNAs). Pseurotin A and chaetominine revealed a concentration and time-dependent inhibition in cellular viability of Huh7 cells as well as significant repression in the proliferation and clonogenic capacities of Huh7 cells, compared to vehicle control. Pseurotin A exhibited more potent effects in halting Huh7 tumorigenic activity than chaetominine. Restoration of TP53, c-Myc, and their downstream tumor suppressor miRNAs; miR-30a, let-7i was achieved by pseurotin A only. Therefore, this study highlights a novel role of alkaloidal compounds from A. fumigatus in controlling the progression of HCC. © 2022 National Information and Documentation Center (NIDOC)