Neurotrophin 3 (NTF3) is a member of the nerve growth factor (NGF) family involved in cancer progression, including medulloblastoma and breast cancer. However, the expression and prognostic value of NTF3 has not been reported in human hepatocellular carcinoma (HCC). Here, we first performed an mRNA expression analysis of the NTF family using the TCGA database and found that NTF3 was significantly downregulated in patients with HCC. Low expression of NTF3 in various HCC cohorts from the GEO database was frequently identified. Consistently, NTF3 protein level was also decreased in HCC tissues as compared with controls. Moreover, survival analysis showed that low NTF3 expression correlated with shorter overall survival (OS) and disease-free survival (DFS) in HCC patients. In addition, there was a positive correlation between the mRNA expression of NTF3 and TrkC in HCC specimens. Generally, these results revealed that low expression of NTF3 predicted an unfavorable clinical outcome. NTF3 may be a diagnostic and prognostic marker in HCC.