Abstract: Objective To investigate the expression of long noncoding RNA linc00261 in hepatocellular carcinoma (HCC) and its correlation with the clinicopathological features and postoperative outcomes of the patients. Methods Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of linc00261 in surgical specimens of HCC and adjacent tissues from 74 patients. The correlation of the expression level of linc00261 in HCC with the clinicopathological parameters of the patients was analyzed using Chi-square test. The Cox’s proportional hazards regression model was used to assess the value of linc00261 in predicting the prognosis of HCC patients after operation. The expression of linc00261 was also examined in 5 HCC cell lines using qRT-PCR. The HCC cell lines MHCC-LM3 and SNU-449 were transfected with small interfering RNAs targeting linc00261 for linc00261 knockdown, and the changes in the cell proliferation, migration and invasion abilities were observed using CCK-8 assay and Transwell assay. Results The expression level of linc00261 in HCC was significantly correlated with AFP (P=0.032), tumor size (P=0.007), microscopic vascular invasion (MVI; P=0.01), and TNM stage (P=002). The patients with lowered expressions of linc00261 in HCC tissues had a significantly shortened tumor-free survival time (P<0.05), and a lowered expression of linc00261 was identified as an independent risk factor affecting postoperative recurrence-free survival time of the patients (P<0.05). In HCC cell lines MHCC-LM3 and SNU-449 cells, linc00261 knockdown obviously promoted the cell migration and invasion (P<0.01) but did not significantly affect cell proliferation (P>0.05). Conclusion Linc00261 may serve as a new prognostic biomarker for predicting the postoperative outcomes of the patients with HCC.