A list of diethynylfluorenes and their gold(I) derivatives have been studied for their antitumor activity as a function of their structure-activity relationships. End-capping the fluoren-9-one unit with gold(I) moieties could significantly strengthen the cytotoxic activity in vitro on three human cancer cell lines with induction of reactive oxygen species generation on Hep3B hepatocellular carcinoma cells and exhibit attractive antitumor activity from in vivo nude mice Hep3B xenograft model with limited adverse effects on vital organs including liver and kidney. © 2009 Elsevier Ltd. All rights reserved.