The PI3K/Akt/mTOR signaling pathway is one of the most frequently dysregulated pathways in cancer.Targeting the PI3K-mediated pathway has been an important strategy for developing novel anticancer agents.In the past decades,more than 40 inhibitors of the PI3K/Akt/mTOR pathway have been developed at different clinical stages.Temsirolimus,everolimus,idelalisib,and copanlisib have been approved for clinical use by the Food and Drug Administration of the United States(FDA).However,the toxic-ity and drug resistance limit their efficiency in the treatment.Novel compounds with greater potency and selectivity,as well as im-proved therapeutic indices with reduced toxicity,are clearly required.Over the past three decades,a lot of bioactive ingredients with anticancer effects by affecting the PI3K-mediated pathways have been found from marine organisms.In the present mini-review,anticancer compounds from marine source that target the PI3K/Akt/mTOR signaling were reviewed.The molecular entities and their modes of action were presented.The marine compounds targeting special factors of the PI3K/Akt/mTOR were highlighted.