Background: In patients with Hepatocarcinoma (HCC), the association between the rapid decline of kidney function and clinical outcomes is still unknown, although kidney-liver crosstalk is comprehensively studied. Objectives: We aimed to investigate the prevalence and determinants of the rapid decline of kidney function and its potential prognostic role and influence on mortality in HCC patients treated by percutaneous injection therapy (PEIT). Methods: This prospective cohort included 114 HCC, with 64.9% males and a mean age of 65.17 years. The rapid decline of kidney function was defined according to kidney disease improving global outcome (KDIGO). The cancer of the liver Italian program (CLIP) score was calculated to predict survival. Multivariable logistic regression analysis for rapid estimated glomerular filtration rate (eGFR) decline was performed after evaluating individual covariates. Multivariable Cox regression models for rapid eGFR decline and mortality were analyzed. Results: During a median follow-up of 31 months, 43.85% of patients presented a rapid decline in eGFR. The baseline eGFR was significantly higher in the group with the rapid decline of kidney function: 86.08 ± 19.17 mL/min/1.73m2 vs. 75.53 ± 25.7 mL/min/1.73 m2 (P = 0.001). The CLIP score (hazard ratio [HR] = 2.55, 95% confidence interval [CI]: 1.70 - 3.84, P < 0.001) was independently associated with rapid eGFR decline. In Cox regression, rapid eGFR decline was independently associated with mortality (HR = 3.49, 95%CI: 1.28 - 9.56, P = 0.015). Conclusions: Nearly half of the HCC patients presented a rapid eGFR decline. The HCC severity evaluated by the CLIP score was an independent predictor of the rapid decline of kidney function. The rapid decline in eGFR was associated with a higher mortality risk in HCC patients, independent of other known risk factors.