A novel Ni-Ca-hydroxyapatite solid acid catalyst was prepared through wet impregnation of Ni(NO3)(2)center dot 6H(2)O on pretreated waste fish scale (PWFS) support, and the catalyst was characterized by TGA, XRD, FESEM, BET, BJH, and FTIR methods. The efficacy of the developed catalyst possessing a specific surface area of 90 m(2)/g, 0.1823 cm(3)/g pore volume, 54.83 nm modal pore diameter, and 7.52 mmol NaOH/g catalyst acidity was evaluated through esterification of free fatty acids (FFAs) of pretreated waste frying soybean oil (PWFSO) in a semibatch reactor. Optimal parametric values for esterification computed using response surface methodology (RSM) corresponding to maximum (i.e., 59.90%) conversion of FFAs to yield FAME (biodiesel) were 0.80 mL/min methanol flow rate, 30 wt % Ni(NO3)(2)center dot 6H(2)O precursor dosage, and 300 degrees C calcination temperature. Subsequent batch transesterification of the unreacted triglycerides present in upstream product catalyzed by calcined fish scale (base catalyst) resulted in an ultimate 98.40% yield of biodiesel.