Background　Altered　lipid　metabolism　is　closely　related　to　the　occurrence　and　development　of　hepatocellular　carcinoma　(HCC).　Carnitine　palmitoyltransferase　1C　(CPT1C)　is　a　member　of　CPT1　family　and　plays　a　key　role　in　cancer　development　and　progression.　However,　how　microRNAs　(miRNAs)　regulate　CPT1C-mediated　fatty　acid　transport　and　oxidation　remains　to　be　elucidated.　Methods　Oil　Red　O　staining,　mitochondrial,　and　lipid　droplets　immunofluorescence　staining　were　used　to　detect　the　functions　of　miR-377-3p　and　CPT1C　in　fatty　acid　oxidation.　Colocalization　of　palmitate　and　mitochondria　was　performed　to　investigate　the　function　of　miR-377-3p　and　CPT1C　in　fatty　acid　transport　into　mitochondria.　Fatty　acid　oxidation　(FAO)　assay　was　used　to　detect　the　function　of　miR-377-3p　and　CPT1C　in　FAO.　Cell　proliferation,　migration　and　invasion　assays　and　animal　experiments　were　used　to　evaluate　the　role　of　miR-377-3p/CPT1C　axis　in　HCC　progression　in　vitro　and　in　vivo.　Immunofluorescence　staining　was　used　to　identify　the　clinical　significance　of　miR-377-3p　and　CPT1C　in　HCC　patients.　Results　MiR-377-3p　inhibits　CPT1C　expression　by　targeting　its　3＇-untranslated　region.　Through　repression　of　CPT1C,　miR-377-3p　suppresses　fatty　acid　oxidation　by　preventing　fatty　acid　from　entering　into　mitochondria　and　decreasing　ATP　production　in　HCC　cells.　Inhibiting　fatty　acid　oxidation　abolishes　the　ability　of　miR-377-3p/CPT1C　axis　to　regulate　HCC　proliferation,　migration,　invasion　and　metastasis　in　vitro　and　in　vivo.　In　HCC　patients,　CPT1C　is　significantly　upregulated,　and　miR-377-3p　expression　and　lipid　droplets　are　negatively　correlated　with　CPT1C　expression.　High　expression　of　miR-377-3p　and　CPT1C　predict　better　and　worse　clinical　outcomes,　respectively.　Conclusions　We　uncover　the　key　function　and　the　relevant　mechanisms　of　the　miR-377-3p/CPT1C　axis　in　HCC,　which　might　provide　a　potential　target　for　the　treatment　of　HCC.