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.