In human cancer, high expression of telomerase is correlated with tumor aggressiveness and metastatic potential. Human telomerase reverse transcriptase (hTERT), which regulates telomere length, can promote tumor development. Most research on hTERT has been focused on its crucial function of telomere maintenance. However, there are many phenomena that cannot be explained by its reverse transcriptase activity. Accumulating evidence suggests that hTERT has functions independent of its protective function at the telomere ends, such as increasing the anti-apoptotic capacity of cells, enhancing DNA repair, maintaining stem cells and regulating gene expression. This review will provide an update on the non-reverse transcriptase activity of hTERT and its contribution to tumor formation, metastasis and cancer stem cell maintenance. Repression of the non-reverse transcriptase activity of hTERT may be a new strategy for tumor therapy.