The traditional reliability analysis method based on probabilistic method requires probability distributions of all the uncertain parameters. However, in practical applications, the distributions of some parameters may not be precisely known due to the lack of sufficient sample data. The probabilistic theory cannot directly measure the reliability of structures with epistemic uncertainty, ie, subjective randomness and fuzziness. Hence, a hybrid reliability analysis (HRA) problem will be caused when the aleatory and epistemic uncertainties coexist in a structure. In this paper, by combining the probability theory and the uncertainty theory into a chance theory, a probability‐uncertainty hybrid model is established, and a new quantification method based on the uncertain random variables for the structural reliability is presented in order to simultaneously satisfy the duality of random variables and the subadditivity of uncertain variables; then, a reliability index is explored based on the chance expected value and variance. Besides, the formulas of the chance theory‐based reliability and reliability index are derived to uniformly assess the reliability of structures under the hybrid aleatory and epistemic uncertainties. The numerical experiments illustrate the validity of the proposed method, and the results of the proposed method can provide a more accurate assessment of the structural system under the mixed uncertainties than the ones obtained separately from the probability theory and the uncertainty theory.