Ensure all equipment is powered off and all gain controls set to zero. Connect the guitar (or other instrument) to the instrument input on the amplifier, and connect the speaker output to the input on the rear of the speaker simulator. This connection will use the heavy-gauge speaker cable that you would normally use to connect your amplifier to its speaker cabinet.
Connect the output of the speaker simulator to the channel input on your mixer. The speaker simulator has both a balanced XLR, and an unbalanced 1/4-inch jack output. Use the balanced output if your mixer has XLR inputs, as it is less susceptible to external noise over long cable runs.
Power on the amplifier first, then the speaker simulator. Set the volume filter on the speaker simulator to the halfway point, then gradually increase the volume on your amplifier until it starts to register on the mixer. Continue increasing the volume until the level is mostly filling the green, without tipping over into the red.
Experiment with the tone shaping controls to find a pleasing speaker sound. Depending on which model of Palmer Speaker Simulator you're using, there are different tone-shaping options. The "Deep/Flat" switch alternates between emulating a large, bass-heavy 4-by-12-inch speaker cabinet, and a small, punchy 2-by-2-inch closed back combo amplifier. The "Bright/Mellow" switch determines the overall tone of the virtual speaker, adding high-end brightness or warming the mid-range. Higher level models also include a number of traditional equalization controls, allowing the independent adjustment of bass, mid-range, and treble.