Imaging modalities provide clinicians with real-time visualization of anatomical regions of interest (ROI) for the purpose of minimally invasive surgery. During the procedure, low-resolution image data are acquired and registered with high-resolution preoperative 3D reconstruction to guide the execution of surgical preplan. Unfortunately, due to the potential large strain and nonlinearities in the deformation of soft biological tissues, significant mismatch may be observed between ROI shapes during pre- and intra-operative imaging stages, making the surgical preplan prone to failure. In an effort to bridge the gap between the two imaging stages, this paper presents a data-driven approach based on artificial neural network for predicting the ROI deformation in real time with sparsely registered fiducial markers. For a head-and-neck tumor model with an average maximum displacement of 30 mm, the maximum surface offsets between benchmarks and predictions using the proposed approach for 98% of the test cases are under 1.0 mm, which is the typical resolution of high-quality interventional ultrasound. Each of the prediction processes takes less than 0.5 s. With the resulting prediction accuracy and computational efficiency, the proposed approach demonstrates its potential to be clinically relevant.