A two-dimensional (2D) partial response maximum likelihood (PRML) detection scheme for misalignment compensation for holographic data storage systems is proposed. In the proposed detection scheme, a misalignment estimator and a predetermined table are added to the conventional 2D PRML scheme to estimate and reflect the effect of misalignment in the vertical and horizontal directions, respectively. In the vertical detection, the misalignment estimator located behind the vertical 2D equalizer and one-dimensional PRML detector estimates the misalignment by the adaptive least-mean-square algorithm (LMS). To improve the estimation accuracy, the misalignment is estimated iteratively by modifying the vertical equalizer coefficients reflecting the estimated misalignment. By considering the estimated misalignment, the vertical 2D equalizer coefficients, horizontal 2D equalizer coefficients, and 2D partial response (PR) target are selected among the predetermined table. In the predetermined table, the vertical and horizontal 2D equalizer coefficients for various misalignments were previously computed on the basis of the misalignment and 2D PR target by the LMS. By employing the horizontal 2D equalizer coefficients and 2D PR target reflecting the misalignment in the horizontal detection, the effect of misalignment is effectively mitigated. Simulation results show that the proposed scheme has more than 3 dB gains than the conventional scheme in the 10% misalignment in the horizontal and vertical directions.