Cancer is a significant contributor to mortality worldwide, posing a significant threat to human life and health. The unique bioactivity, ability to precisely control drug release, and minimally invasive properties of hydrogels are indispensable attributes that facilitate optimal performance in cancer therapy. However, conventional hydrogels lack the ability to dynamically respond to changes in the surrounding environment, withstand drastic changes in the microenvironment, and trigger drug release on demand. Therefore, this review focuses on smart-responsive hydrogels that are capable of adapting and responding to external stimuli. We comprehensively summarize the raw materials, preparation, and cross-linking mechanisms of smart hydrogels derived from natural and synthetic materials, elucidate the response principles of various smart-responsive hydrogels according to different stimulation sources. Further, we systematically illustrate the important role played by hydrogels in modern cancer therapies within the context of therapeutic principles. Meanwhile, the smart hydrogel that uses machine learning to design precise drug delivery has shown great prospects in cancer therapy. Finally, we present the outlook on future developments and make suggestions for future related work. It is anticipated that this review will promote the practical application of smart hydrogels in cancer therapy and contribute to the advancement of medical treatment.