Anaerobic hybrid reactor (AHR) using integrated benefits from sludge bed and fixed bed reactors’ key features has been developed for wastewater treatment and biogas production from Tapioca starch industry in Thailand for more than a decade. Furthermore, a number of feasibility studies regarding both laboratory-scale and pilot-scale hybrid reactor performances have also represented that the design of this bioreactor is likely practical and is promising for biogas generation and organic compound reduction from palm oil mill effluent (POME) which contained higher chemical oxygen demands (COD) and suspended solids (SS) contents than tapioca starch wastewater. The objective of this study was to investigate efficiency of an industrial-scale anaerobic hybrid reactor with 4,900 m³ working volume on POME treatment and biogas production in order to archive more detail on full-scale plant operation. Results from approximately 3.5 years-study showed that the hybrid reactor could not run at organic loading rate (OLR) and hydraulic retention time (HRT) as prior studies relating to uncertain production plan of the palm oil mill. Nevertheless, the reactor performance depicted its COD and SS removal efficiency as high as 80% and 60%, respectively, when it was operated in the range of OLR as high as 3.0 kg COD/m³.day and 20 days HRT. Average biogas yield was approximately 0.42 ± 0.08 m³/kg CODremoved with 57.5 ± 1.4 % CH4 content. The estimation on economic feasibility based on the derived operating data suggested that the anaerobic hybrid reactor could be applied as high potential wastewater treatment and biogas production system for palm oil mill industry. The continuously produced biogas could be supplied as renewable fuel for running a gas engine to generate electricity upto 1 MW. Refer to income from selling electricity to Thailand’s national grid, the palm oil mill could recover its investment on this project with approximately 3.2 years-payback period.