Hepatocellular carcinoma (HCC) ranks among the most prevalent types of cancer globally. Zinc finger protein 169 (ZNF169) holds significant importance as a transcription factor, yet its precise function in HCC remains to be elucidated. This study aims to examine the clinical importance, biological functions, and molecular pathways associated with ZNF169 in the development of HCC. The study employed lentiviral transduction for ZNF169 overexpression and the use of small interfering RNAs (siRNAs) to suppress its expression. ZNF169 was upregulated in HCC tissues and cell lines. Additionally, HCC patients exhibiting elevated ZNF169 levels experienced reduced overall survival, shorter disease-free survival, and diminished progression-free survival. Silencing of ZNF169 inhibited cell proliferation, migration, and cell cycle progression. Whereas ectopic expression of ZNF169 promoted HCC progression in vivo and ex vivo. Subsequently, Pearson analysis results showed that cyclin-dependent kinase 19 (CDK19) was positively correlated with ZNF169 levels in HCC using TCGA dataset. Luciferase assay findings indicated a potential interaction between ZNF169 and CDK19 promoter. Additionally, our data showed that CDK19 expression levels were elevated in HCC tissues, and patients with higher CDK19 expression faced a poorer prognosis. Furthermore, recovery experiments demonstrated that CDK19 could reverse the impact of ZNF169 on HCC cell amplification. Our findings indicate that ZNF169 promotes HCC progression by upregulating CDK19, highlighting its role as a therapeutic target or prognostic biomarker for HCC.