To investigate the effect of serine-Arginine protein kinase 1 (SRPK1) on Epithelial mesenchymal transformation (EMT) in HepG2 cell line.Methods The differential expression of SRPK1 mRNA among liver hepatocellular carcinoma (LIHC) and normal samples and paired adjacent tissues were compared, and the relationship between the expression of SRPK1 and the clinicopathological characteristics of liver cancer including overall survival, clinical stage, pathological stage, TP53 mutant, race, sex, age, weight were analyzed by Ualcan and TIMER database.Immunohistochemical data from HPA database were used to verify the difference of SRPK1 protein expression between LIHC tissues and normal controls.HepG2 cells with SRPK1 overexpression and inhibition were constructed and divided into the SRPK1 group, Vector group, shRNA group, and Scramble group.The protein level of SRPK1 was detected by Western blot.The differential protein expressions of EMT molecular markers E-cadherin and Vimentin were detected by Western Blot and immunofluorescence.Nucleoplasmic protein isolation was used to compare the degree of β-catenin protein transport from Cytoplasm to Nucleus.GEPIA2 database was used to analyze the correlation between SRPK1 and Wnt/β-catenin pathway downstream genes including Twist, MYC and MMP9 in LIHC.Real-time PCR was used to verify the effect of SRPK1 on Twist, MYC and MMP9 expressions.Results The expression of SRPK1 in LIHC tissues was significantly higher than that in normal control and paired paracancer samples (P＜0.05), and increased with worse stage and grade (P＜0.05).The overall survival of high SRPK1 expression was lower than that of low SRPK1 expression (P=0.035), and the expression of SRPK1 in TP53 mutant group was higher than that in the TP53 non-mutant group (P＜0.05).There was no difference among different races, genders, ages and weights (P＞0.05).SRPK1 overexpressed HepG2 cells showed decreased E-cadherin and increased Vimentin (P＜0.05).Consistently, E-cadherin increased and Vimentin decreased in SRPK1 inhibitied cells (P＜0.05).SRPK1 was positively correlated with Twist, MYC and MMP9 expression in LIHC (P＜0.05).The level of β-catenin protein in nucleus and the expression of Twist, MYC and MMP9 increased in SRPK1 overexpressed cells (P＜0.05), and which were decreased in SRPK1 inhibitied cells inversely (P＜0.05).Conclusion SRPK1 may promote EMT activation in HepG2 cells through Wnt/β-catenin pathway activation