This work deals with the alkaline hydrolysis of brewer's spent grain (BSG) for the extraction of ferulic and p-coumaric acids, compounds of considerable interest for applications in the food, health, cosmetic, and pharmaceutical industries. A 23 full factorial design with three replicates at the center point was used to investigate the simultaneous effects of the variables: NaOH concentration (1.0, 1.5 and 2.0%, w/v), temperature (80, 100 and 120 °C), and reaction time (30, 60 and 90 min), on the alkaline hydrolysis. The assays were performed using a solid:liquid ratio of 1:20 (w/w). The Student's t-test revealed a positive influence (p < 0.05) of all the studied variables on the ferulic and p-coumaric acids extraction from BSG. Linear models were well fitted (R2 > 0.90) to the experimental data to describe the extraction of these acids as a function of the operational variables employed. The best alkaline hydrolysis conditions consisted in using a 2% NaOH concentration, at 120 °C for 90 min. Under these conditions, a liquor containing 145.3 mg/l ferulic acid and 138.8 mg/l p-coumaric acid was obtained. These values corresponded to 9.65 mg ferulic acid and 9.22 mg p-coumaric acid per gram of solubilized lignin.