The manifestation of hepatocellular carcinoma (HCC) involves a multi-factor, multi-step and complex process. Due to the lack of early prediction indices, numerous patients are diagnosed in their late stage. Recently, research in the field of non-coding RNAs (ncRNAs) has changed the original idea that ncRNA genes are just ̔noise̓. Cumulative evidence shows that long non-coding RNAs (lncRNAs) among ncRNAs play an increasingly important role in epigenetics, pre-transcription and post-transcription. In the present study, we focused on the expression pattern of lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) and its clinical significance in HCC diagnostics. We analyzed the expression, its association with clinical characteristics and the diagnostic value of SPRY4-IT1 using HCC tissues, cell lines and plasma. The levels of SPRY4-IT1 were upregulated in HCC and were associated with tumor differentiation (r=0.249, p=0.039), tumor size (r=0.258, p=0.024) and tumor-node-metastasis (TNM) stage (r=0.287, p=0.015). Meanwhile, the sensitive of SPRY4-IT1 was 87.3% in differentiating HCC patients from controls. Our data suggest that SPRY4-IT1 plays a critical role in HCC tumorigenesis and may be considered as a potential diagnostic indicator in HCC.