The development of chemotherapy drugs has promoted anticancer treatment, but the effect on tumours is not clear because of treatment resistance; thus, it is necessary to further understand the mechanism of cell death to explore new therapeutic targets. As a new type of programmed cell death, ferroptosis is increasingly being targeted in the treatment of many cancers with clinical drugs and experimental compounds. Ferroptosis is stimulated in tumours with inherently high levels of ferrous ions by a reaction with abundant polyunsaturated fatty acids and the inhibition of antioxidant enzymes, which can overcome treatment resistance in cancers mainly through GPX4. In this review, we focus on the intrinsic cellular regulators against ferroptosis in cancer resistance, such as GPX4, NRF2 and the thioredoxin system. We summarize the application of novel compounds and drugs to circumvent treatment resistance. We also introduce the application of nanoparticles for the treatment of resistant cancers. In conclusion, targeting ferroptosis represents a considerable strategy for resistant cancer treatment.