A large number of researches have shown that circular RNA (circRNA) is new hope for the diagnosis or treatment of tumors, including liver cancer (LCa). However, it remains largely unclear the role of circRNA in the progression of LCa and its molecular mechanism. GSE164803 microarray dataset was applied to identify dysregulated circRNAs in LCa and noncancerous tissues. CircTUBGCP5 (hsa_circ_0034049) was selected for further research. Biological functions of circTUBGCP5 were investigated by EdU, colony formation, flow cytometry, glucose consumption and lactate production assay, and in vivo tumorigenesis. RNA pull-down assay and dual-luciferase reporter assay were used to investigate the interaction between circTUBGCP5, miR-144-3p, and ACSL4. We demonstrated that circTUBGCP5 was significantly up-regulated in LCa tissues and cells. CircTUBGCP5 promoted LCa cell proliferation, anti-apoptotic ability, glycolysis, and tumorigenesis at least partially by sponging miR-144-3p to regulate ACSL4 protein level. In conclusion, circTUBGCP5 is a forceful contributor to malignant behaviors and glycolysis of LCa via modulating the circTUBGCP5/miR-144-3p/ACSL4 axis, which has provided a target for the diagnosis and treatment of LCa patients.