A rapid decline in renal function is associated with high cardiovascular morbidity and mortality, and therefore it is important to identify those at high-risk of rapid renal function decline. The relationship between liver function and renal function is unclear. Therefore, in this longitudinal study, we aimed to investigate associations between liver function and rapid renal function decline. A total of 27,116 participants were enrolled from the Taiwan Biobank and followed for 3.8 years. A rapid decline in renal function was defined as a decline in estimated glomerular filtration rate (eGFR) of ≥25%. Binary logistic regression analysis was used to identify associations between liver function parameters (glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, albumin, α-fetoprotein [AFP], total bilirubin, and gamma-glutamyl transpeptidase) and eGFR decline ≥ 25%. The rate of eGFR decline of ≥25% was 4.7%. Multivariable analysis showed that low albumin (odds ratio [OR], 0.173; p < 0.001), high AFP (OR, 1.006; p = 0.010), and low total bilirubin (OR, 0.588; p < 0.001) were significantly associated with eGFR decline ≥ 25% in all study participants. After excluding abnormal liver function, low albumin (OR, 0.189; p < 0.001), high AFP (OR, 1.007; p = 0.011), and low total bilirubin (OR, 0.569; p = 0.001) were still significantly associated with an eGFR decline of ≥25%. The results of this large population-based cohort study showed associations between low albumin, low bilirubin, and high AFP with a rapid renal function decline. A greater understanding of potential risk factors for a rapid decline in renal function may help to reduce the burden of renal failure in this high-risk population.