In this paper, a new reliability assessing method for structures influenced by both aleatory and epistemic uncertainty simultaneously is developed. To handle hybrid types of uncertainties, chance theory is introduced to define a new hybrid reliability index. By mathematical derivation and theorems proofs, the new index is showed to be effective and compatible with hybrid types of uncertainties. Correspondingly, a generalized first-order second-moment (GFOSM) algorithm is established for practical reliability assessment of structures with hybrid uncertainties. Based on the first two moments of basic variables, the GFOSM method can perform fast and effective reliability assessment without large-scale integration operations and can be considered as an extension and expansion of the traditional FOSM method. Two numerical cases further illustrate the effectiveness and practicability of the proposed method from different perspectives.