Saffron is a spice that its preventive and curative effects against cancer have been seen in the studies. However, there are some worries about saffron toxicity against normal cells. This is the first study that has reviewed the toxicity of saffron extract and its’ constitutes on normal and cancer cells. To search English studies, the articles of Pub Med, Science Direct and Google Scholar databases, and to search Persian articles SID and Magiran databases database were searched. Totally, 65 English and 5 Persian articles have used for the review. Saffron has a selective toxicity against cancer cells, with mechanisms including inhibition of RNA and DNA synthesis and increasing apoptosis. Crocin has considered as the most important anticancer agent of saffron the effect may be due to make changes in gene expression and due to apoptosis induction in cancer cells. Crocetin has an inhibitory effect on the growth of cancer cells. The effect of crocetin may be due to reduced synthesis of DNA, RNA and protein in neoplastic cells, inhibition of RNA polymerase II, and interaction with histone H1 and H1-DNA structures. Saffron and its’ crocin and crocetin have also shown anticancer and cancer-preventive effects in animal models of cancer. In the other hand, The Lethal dose, 50% (LD50) for the saffron and its’ constitutes against normal cells is very high. So, the results suggests that saffron extract and its crocin and crocetin have a selective toxicity against cancer cells and cancer preventive functions. However, Saffron and its’ constitutes toxicity against normal cells is quite low and they are even non-toxic in oral administration.