Unlike the low-Earth orbit (LEO) project, space radiation, mainly coming from galactic cosmic radiation (GCR) and solar particle event (SPE), has been generally considered to be one of the most important health risk factors for astronauts in manned deep space exploration missions. In fact, space radiation environment in deep space is substantially different from that in low Earth orbit, in which high-energy protons and heavy nuclei provide the main contribution to the equivalent dose and health risk. Both the total equivalent dose and health risk in deep space are significantly higher than those in LEO missions, which may exceed the permissible radiation exposure limits in the career of astronauts. And, health risks from space radiation exposure remain a primary concern for manned deep space explorations. Space radiation protection is an important strategy to reduce astronauts’ risks of damage and disease induced by space radiation and ensure their health and safety in manned deep space exploration missions. Therefore, space radiation protection is considered to be an important technical problem to be solved in the further manned spaceflight project. However, the complexity and particularity of space radiation environment in manned deep space exploration missions make space radiation protection extremely difficult. Based on the analysis of space radiation environment characteristics in manned deep space exploration missions, this review systematically summarizes and analyzes the current research progresses of space radiation protection, including physical protection and biomedical protection. In general, the physical protection refers to the passive shielding and acitve shielding. The passive shielding of materials with different thickness is the simplest and feasible physical countermeasure to deal with deep space radiation, especially in the case of SPE occurrences. The passive shielding technologies were raised and reviewed from four aspects, including radiation shielding performance indexes and their applications in new material selections, manned spacecraft radiation shielding, personal radiation shielding, and astral surface soil radiation shielding. However, the passive shielding is problematic for GCR due to the penetration of primary high-energy particles, the production of secondary radiation and the mass constraints of manned spacecraft. While, active shielding, involving the generation of electromagnetic fields to deflect space radiation, is a promising and interesting technical improvement to overcome challenging technical hindrance to prevent GCR. But different kinds of active shielding technologies, such as electrostatic shielding, plasma shielding, confined and unconfined magnetic field shielding, have not been applicable in practical cases. Moreover, a series of radioprotectors and radiomitigators in the biomedical protection, including (1) antioxidants, (2) inhibitors of various pathways, (3) cytokines, chemokines, growth factors and hormones, (4) protein molecules, (5) cellular therapeutic agents, and (6) plant derived products, were also summarized and reviewed. Most radioprotectors and radiomitigators are currently being researched and developed under early preclinical phase, and have not been approved by the food and drug administrations. At the same time, the deficiency of some present radioprotectors and radiomitigators, such as the unclear biomedical mechanisms and unavoidable side-effects, limited the popularity in actual applications. In a word, the review points out that the current space radiation protection technologies still face a series of problems and challenges, and puts forward the key technologies and countermeasures of the current space radiation protection. The summary and analysis of the critical challenges and key countermeasures of space radiation protection are of great significance for the follow-up researches and provide a theoretical basis and a solution for the implementation of manned deep space exploration mission.