Analyses of human reliability during manned spaceflight are crucial because human error can easily arise in the extreme environment of space and may pose a great potential risk to the mission. Although various approaches exist for human reliability analysis (HRA), all these approaches are based on human behavior on the ground. Thus, to appropriately analyze human reliability during spaceflight, this paper proposes a space-based HRA method of quantifying the human error probability (HEP) for space missions. Instead of ground-based performance shaping factors (PSFs), this study addresses PSFs specific to the space environment, and a corresponding evaluation system is integrated into the proposed approach to fully consider space mission characteristics. A Bayesian network is constructed based on the cognitive reliability and error analysis method (CREAM) to model these space-based PSFs and their dependencies. By incorporating the Bayesian network, the proposed approach transforms the HEP estimation procedure into a probabilistic calculation, thereby overcoming the shortcomings of traditional HRA methods in addressing the uncertainty of the complex space environment. More importantly, by acquiring more information, the HEP estimates can be dynamically updated by means of this probabilistic calculation. By studying 2 examples and evaluating the HEPs for an International Space Station ingress procedure, the feasibility and superiority of the developed approach are validated both mathematically and in a practical scenario.