Updated project metadata. Hypnea musciformis is a red macroalga that is widely distributed in tropical and subtropical regions. It is known to contain various bioactive compounds, including sulfated polysaccharides, flavonoids, and phlorotannins. Recent studies have investigated the potential anticancer effects of extracts from Hypnea musciformis demonstrating their have cytotoxic effects on various cancer cell lines. The anticancer effects of these extracts are thought to be due to the presence of bioactive compounds, which have been shown to have antitumor and immunomodulatory effects. However, further studies are needed to fully understand the molecular mechanisms that underlie these anticancer effects and to determine their potential as therapeutic agents for cancer treatment. We have performed transcriptome and proteome analysis in liver and colon cancer human cell lines following treatment with Hypnea musciformis macroalgae extracts to characterize its anti-tumor effect in detail at the molecular level and to link transcriptome and proteome responses to the observed phenotypes in vitro. We have identified that treatment with the macroalgae extract triggers p53-mediated response at the transcriptional and protein level in liver cancer cells, in contrast to colon cancer cells in which the effects are associated with metabolic changes. Overall, the available evidence suggests that extracts from Hypnea musciformis have the potential to serve as a source of anticancer agents in liver cancer cells through the activation of a p53-mediated anti-tumor response that is linked to inhibition of cellular proliferation and induction of apoptosis.