Local scour significantly reduces the bearing capacity of pile foundations by removing soil around the piles. Due to the directional nature of waves and currents, scour holes exhibit asymmetry. To clarify the lateral response of horizontally loaded pile foundations under local asymmetric scour conditions, an asymmetric scour hole model was proposed. A three-dimensional finite element model was established using ABAQUS software and validated through comparison with experiments. A systematic parameter analysis was then conducted to study the lateral responses of pile foundations under varying asymmetric scour ratios, maximum scour depth, scour hole angles, and load directions. A modified p-y curve model under asymmetric scour conditions was also developed. The results indicate that as the asymmetric scour ratio decreases, maximum scour depth increases, and the scour hole angle decreases, the horizontal bearing capacity and maximum bending moment decrease, while the maximum soil resistance increases. The positions of the maximum bending moment and soil resistance, as well as the rotation center of the pile, shift towards the pile base. Due to the asymmetry of the scour hole, there are significant differences in the lateral responses of the pile foundation when loaded along the positive and negative y-axis directions, and these differences become more pronounced with increasing scour depth and increasing asymmetric scour ratio.