The　existence　of　cancer　stem　cells　(CSCs)　is　considered　to　be　the　main　reason　for　chemoresistance,　metastasis　and　the　ultimate　failure　of　treatment　in　hepatocellular　carcinoma　(HCC　).　However,　there　are　a　few　chemical　agents　that　may　inhibit　CSCs.　The　present　study　identified　that　4,4＇-bond　secalonic　acid　D　(4,4＇-SAD),　a　compound　isolated　from　the　marine-derived　fungus　Penicillium　oxalicum,　inhibited　the　growth　of　side　population　(SP)　cells　isolated　from　human　liver　cancer　cell　lines　PLC　/PRF/5　and　HuH-7　by　attenuating　the　expression　of　ATP-binding　cassette　superfamily　G　member　2.　Furthermore,　the　results　of　wound　healing,　Transwell,　western　blotting　and　reverse　transcription-quantitative　PCR　assays　demonstrated　that　4,4＇-SAD　suppressed　the　invasion　and　migration　of　SP　cells　by　downregulating　matrix　metallopeptidase　9　(MMP-9)　and　upregulating　the　antagonist　tissue　inhibitor　of　metalloproteinases　1　in　vitro.　Moreover,　in　vivo　study　results　found　that　4,4＇-SAD　had　anti-lung　metastasis　efficacy　via　the　decrease　of　MMP-9　expression　in　the　H22　HCC　model　of　Kunming　mice.　Therefore,　the　present　study　identified　the　potential　of　4,4＇-SAD　as　a　promising　candidate　for　the　treatment　of　advanced　liver　cancer.　©　2020　Spandidos　Publications.　All　rights　reserved.