MicroRNAs (miRNAs) are small non-coding regulatory RNAs that are often dysregulated during carcinogenesis. Downregulation of let-7 miRNA in many human cancers indicates its role in tumourigenesis. This study evaluated the levels of let-7c miRNA, using real-time reverse transcription-polymerase chain reaction, between 32 hepatocellular carcinoma (HCC) tissues and matched normal adjacent tumour tissues within the context of the patient's clinical pathology. Levels of let-7c miRNA were significantly lower in HCC tissues than in corresponding normal adjacent tumour tissues and there was a correlation between the downregulation of let-7c and poor tissue differentiation in HCC. There was no correlation between let-7c miRNA levels and other clinicopathological factors, such as patient age, sex, hepatitis B virus status, α-fetoprotein levels, tumour size, tumour number, the presence of cirrhosis, liver envelope invasion or portal vein thrombosis. These data suggested that let-7c microRNA may play a role in regulating HCC cell differentiation.