LncRNA was a newly identified lncRNA which has never been studied in cancers. Whether PITduanyu1535-AS1 participated in the development of hepatocellular carcinoma (HCC) is obscure. Given the coaction of lncRNAs and miRNAs to carcinogenesis, the purpose of the present research is to inquire how PITduanyu1535-AS1 affects HCC progression. Firstly, PITduanyu1535-AS1 was observed to be heightened in HCC tissues. Then function assays proved that overexpressing or silencing PITduanyu1535-AS1 could manipulate the proliferation and motility of HCC cells. Besides, PITduanyu1535-AS1 was located in the cytoplasm. Among the candidate miRNAs of miR-876-5p was an obvious target. Moreover, mechanism experiments validated that PITduanyu1535-AS1 modulated WNT5A expression by targeting miR-876-5p. Rescue experiments affirmed that WNT5A silencing rescued the miR-876-5p suppression-induced cellular processes in Hep3B cells. And in vivo experiments determined that PITduanyu1535-AS1 regulated HCC progression in vivo via miR-876-5p/WNT5A pathway. In conclusion, this work shed lights on the modulatory mechanism of axis in HCC, which might be pivotal for exploring effective diagnostic biomarkers and treatment strategies for HCC patients.