Milk processing industries consume significant volumes of sustainable water during processing and operating steps to meet hygienic requirements. Therefore, such industries are recognized as a potential source for producing large volume of contaminated water which generally contains biodegradable matters, and are subsequently suitable to be biologically treated. Based on this, many researchers have been moving towards milk processing wastewater (MPW) treatment via biological approaches. In present study, the performance of a single stage flexible fibre biofilm reactor (SS-FFBR) in mitigation of organic loading of the MPW was assessed. The performance of SS-FFBR in terms of the biological treatment was statistically modelled and analysed in terms of HRT and CODin by employing response surface methodology (RSM). From the results, it is clear increase in HRT and decrease in the CODin led to incrementing the COD removal percentage. In addition, a significant mutual interaction occurs between the variables and other responses. The optimum removal was reported at an HRT of 8 h and CODin of 3922 mg/L corresponded to high OLR of 11.67 kg COD/m3 d. The experimental results were in good agreement with model prediction.