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Background The up-regulation of KIF3A possibly predicts the dismal prognostic outcome of hepatocellular carcinoma (HCC). The present work is focused on investigating KIF3A’s function in the growth and migration of HCC cells. Methods KIF3A expression and its role in predicting HCC prognosis were assessed using the TCGA and Genotype-Tissue Expression (GTEx) databases. KIF3A detection conditions in HCC patients were studied using an immunohistochemical panel. siKIF3A was created and then transfected into HepG2 HCC cells. Cell proliferation was examined with the use of the EDU and CCK8. Using the scratch wound healing assays, cell migration was assessed. RT-PCR and Western-blot (WB) assays were adopted for evaluating the expression of genes and proteins. Results KIF3A expression increased in HCC tissues as compared to matched non-carcinoma samples, and it was tightly associated with poor survival and risk factors (Ps < 0.05). KIF3A knockdown hindered the proliferation and migration of HCC cells (Ps < 0.05). KIF3A silencing reduced RelA (NF-κBp65) expression, thus, affecting the activity of HCC cells (Ps < 0.05). Conclusion In this study, the oncogene of hepatocellular carcinoma is KIF3A. Silencing KIF3A inhibited HCC cell growth and migration by suppressing the NF-κB signal pathway. KIF3A was identified as a potential new anti-HCC therapeutic target.