It has been reported that SEMA3B-AS1 is a tumor-suppressive lncRNA in gastric cardia adenocarcinoma. We explored the possible involvement of SEMA3B-AS1 in hepatocellular carcinoma (HCC). We found that SEMA3B-AS1 was downregulated in HCC tissues compared with noncancer tissues and was not affected by hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In addition, SEMA3B-AS1 expression was not affect by cancer development, and low SEMA3B-AS1 levels were closely correlated with poor survival. SEMA3B-AS1 in HCC tissues was inversely correlated with microRNA (miR)-718 and positively correlated with PTEN. In HCC cells, SEMA3B-AS1 overexpression resulted in upregulated, while miR-718 overexpression resulted in downregulated phosphatase and tensin homolog (PTEN) expression. In addition, miR-718 overexpression attenuated the effects of SEMA3B-AS1 overexpression. SEMA3B-AS1 and PTEN overexpression resulted in a reduced proliferation rate of HCC cells, while miR-718 overexpression resulted in an increased rate. In addition, miR-718 overexpression attenuated the effects of SEMA3B-AS1 overexpression. Therefore, miR-718 may mediate the indirect interaction between lncRNA SEMA3B-AS1 and PTEN to regulate the proliferation of hepatocellular carcinoma cells.