In recent years, increasing evidence has confirmed that exosomal circular RNAs (circRNAs) serve a crucial role in the prognostic prediction and diagnosis of liver cancer (LC). The present study compared the expression patterns of exosomal circRNAs during transarterial chemoembolization (TACE). CircRNA sequencing analysis identified 390 differentially expressed circRNAs between the prior TACE and following the first TACE operation groups and 489 differentially expressed circRNAs between the prior to TACE and following the second TACE operation groups. Gene Ontology analysis of the differentially expressed circRNAs demonstrated that they were associated with fatty acid metabolism, receptor binding and membrane protein complexes. Kyoto Encyclopedia of Genes and Genomes pathway analysis predicted that protein digestion and absorption pathways were activated following TACE. A novel gene was screened out; hsa-circRNA-G004213 (circ-G004213) was significantly upregulated following TACE (fold change >10, P<0.01). Further analysis found circ-G004213 significantly increased the cisplatin sensitivity of HepG2 cells and positively associated with the prognosis of tumor-bearing mice. Based on the potential downstream miRNAs and mRNAs, the circRNA-miRNA-mRNA network was constructed. It was demonstrated that circ-G004213 regulated cisplatin resistance via the miR-513b-5p/PRPF39 axis. Finally, the present study confirmed that circ-G004213 was positively associated with the prognosis of patients with LC following TACE. Therefore, circ-G004213 may be used as an indicator for predicting the efficacy of TACE.