This paper presents a maximum power point tracking (MPPT) of a scale-up pressure retarded osmosis (PRO) based osmotic power generator. Inspired by the well-known MPPT in photovoltaic (PV) array, two algorithms, perturb & observe (P&O) and incremental mass-resistance (IMR) method, are investigated. Using a series of simulations, both the algorithms are demonstrated to be capable of tracking the maximum power point (MPP) and capturing the transitions between varied MPPs due to the fluctuations of operating temperature. However, in both cases the trade-off between the rise time and the oscillation is found requiring further consideration on the selection of the step-size for perturbation pressure or incremental pressure. In order to improve the performance of the MPPT, furthermore, an optimum model-based controller (OMC) is used to estimate the initial optimum pressure for the MPPT in a scale-up PRO process. It is found that with OMC, the performance of the MPPT is improved significantly. Finally, a strategy to operate and coordinate the MPPT and OMC to deal with the rapid variations of the salinities are proposed and evaluated in terms of individual variation of the concentration or flow rate and co-variation of the both. The simulations demonstrate the preferred performance of the proposed strategy to adjust the operation subject to the rapid changes of the salinities. Crown Copyright (C) 2015 Published by Elsevier Ltd. All rights reserved.