Joystick calibration usually needs to be run only one time, when you've first installed HeliSimRC. Or when you've obtained a new controller. Its function is to allow HeliSimRC to record the center position, and range of all the input channels from your control box.
There are two steps to perform calibration.
First, center the control sticks in their travel. Use your mouse to click the OK button.
Second, move all the sticks through their entire range. I like to move the sticks around in circles several times.
While you're doing this, you should see the indicators moving along with the sticks.
Click OK again, and you're done.