To study the expressions of hypoxia-inducible factor-1α (HIF-1α) and tumor metastasis suppressor gene (KISS-1) in patients with liver cancer and to analyze the correlation between HIF-1α and KISS-1 and liver cancer. 20 normal liver tissues and 30 liver cancer tissues in our hospital were selected. The expressions of HIF-1α and KISS-1 in normal liver tissues and liver cancer tissues were detected via immunofluorescence assay. The mRNA expressions of HIF-1α and KISS-1 in normal liver tissues and liver cancer tissues were detected via reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of HIF-1α and KISS-1 in normal liver tissues and liver cancer tissues were detected via Western blotting. Differences of HIF-1α and KISS-1 expressions in normal liver tissues and liver cancer tissues were analyzed using SPSS 17.0 statistical software. Immunofluorescence assay, RT-PCR, and Western blotting, showed that HIF-1α was highly expressed in liver cancer tissues, and its expression level was significantly higher than that in normal liver tissues. However, the expression of KISS-1 in normal liver tissues was significantly higher than that in liver cancer tissues. The results of analysis of variance showed that the differences of HIF-1α and KISS-1 expressions in normal liver tissues and liver cancer tissues were statistically significant (p<0.01). The abnormal expressions of HIF-1α and KISS-1 are closely related to the development and progression of liver cancer, indicating that HIF-1α and KISS-1 have important research values in liver cancer, and the expressions of HIF-1α and KISS-1 can be used as the index of deterioration degree of liver cancer, providing a new clinical basis for diagnosis and treatment.