OBJECTIVE The literature is sparse on the association between serum liver fibrosis markers and the development of hepatic decompensation in patients with compensated cirrhosis. We aimed to assessed whether the serum liver fibrosis markers are predictive of the occurrence of hepatic decompensation. METHODS We ascertained 688 cirrhotic patients with varying etiologies, between December 2015 to December 2019. Serum hyaluronic acid (HA), laminin (LN), collagen IV (CIV), and N-terminal propeptide of type III collagen (PIIINP) levels were measured at enrollment. All subjects were followed for at least 6 months for occurrence of hepatic decompensation. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of hepatic decompensation during follow-up. RESULTS During a median follow-up of 22.0 (13.0-32.0) months, decompensation occurred in 69 (10.0%) patients. Multivariate analysis indicated that higher LN (HR: 1.008, 95% confidence interval [CI]: 1.002-1.014, P = 0.011) and CIV (HR: 1.004, 95% CI: 1.001-1.007, P = 0.003) levels were independently associated with hepatic decompensation. Furthermore, patients in the tertile 2 and tertile 3 groups for CIV levels had HRs of 4.787 (1.419, 16.152) (P = 0.012) and 5.153 (1.508, 17.604) (P = 0.009), respectively, for occurrence of decompensation event compared with those in the tertile 1 group. CONCLUSIONS Serum liver fibrosis markers, particularly in CIV, appeared to be reliable biomarkers of disease progression and liver decompensation in patients with compensated cirrhosis with varying etiologies.