We hypothesised that liver-derived mRNA, such as albumin (ALB) mRNA, would be released into human plasma as a result of liver cell death. We genotyped the ALB mRNA molecules in plasma and whole blood of liver or bone marrow transplantation recipients by RNA-single nucleotide polymorphism analysis. The plasma and whole blood ALB mRNA genotypes were compared with the DNA genotypes in the recipients and donors. Our data revealed that ALB mRNA in plasma was liver-derived, while tissue compartments other than the liver also contributed to the ALB mRNA detected in whole blood. We then used a reverse transcription quantitative real-time PCR assay to show that the plasma ALB mRNA concentrations were elevated in patients with hepatocellular carcinoma, cirrhosis or chronic hepatitis B than healthy controls. Only 21.5% of patients with liver pathologies had elevated alanine transaminase (ALT) when 73.8% of them had elevated plasma ALB mRNA concentrations. Only 49% of the hepatocellular carcinoma patients had elevated serum alpha-fetoprotein, while 91.4% had elevated plasma ALB mRNA concentrations. Liver-derived plasma mRNA may become a new class of biomarkers for the sensitive detection of liver diseases. Acknowledgement Supported by the Hong Kong Research Grants Council Earmarked Research Grant (CUHK463207).