We aimed to investigate whether lncRNA CYTOR could sponge miR-125b-5p to affect hepatocellular carcinoma (HCC) cells through targeting KIAA1522. The expression of CYTOR, miR-125b-5p and KIAA1522 in HCC cells was detected by Real-time quantitative polymerase chain reaction (RT-qPCR) analysis. KIAA1522 expression in HCC tissues was detected by immunohistochemistry. The proliferation, cell cycle and apoptosis of HCC cells after transfection were respectively detected by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, and related protein expression was determined by Western blot analysis. As a result, The Cancer Genome Atlas (TCGA) database indicated that expression of CYTOR and KIAA1522 was increased in HCC tissues and high expression of CYTOR and KIAA1522 was related to worse overall survival. MiR-125b-5p expression was decreased in HCC tissues, which was negatively correlated with the expression of CYTOR and KIAA1522. The proliferation and cell cycle of HCC cells were suppressed by CYTOR interference while promoted by miR-125b-5p interference and KIAA1522 overexpression. The apoptosis of HCC cells was promoted by CYTOR interference while inhibited by miR-125b-5p interference and KIAA1522 overexpression. In conclusion, CYTOR interference suppressed the proliferation and cell cycle, and promoted the apoptosis of HCC cells by regulating the miR-125b-5p/KIAA1522 axis.