To study the seismic performance of reinforced concrete (RC) columns failed in flexure-shear, cyclic loading tests were carried out on twenty-four RC columns with different design parameters. The effects of shear span ratio, axial load ratio and volumetric stirrup ratio (spacing of transverse reinforcement) on the failure modes and seismic performance of columns were studied. Based on the test data analysis, the calculation formulas for predicting the cracking, yielding and failure loads, as well as corresponding displacements, of RC columns failed in flexure-shear mode were developed, and then the trilinear skeleton curve model of RC columns with flexure-shear failure was established according to three feature points. The study results show that the seismic responses of RC columns failed in flexure-shear mode are dominated by flexure before the displacement reaches 2Δy-4Δy. The hysteretic loops are plump. But the bearing capacity may be lost suddenly due to shear failure. The skeleton curve model presented in this study is dependent mostly on three feature points of columns with flexure-shear failure, which is simple and computationally efficient. The predicted skeleton curves match the experimental data with adequate accuracy, and the model can be used to simulate the load-deformation curve of RC columns with flexure-shear failure subjected to seismic excitation.