An apparatus and a method for Direct Current (DC) offset calibration in a signal transmission device of a wireless communication system are provided. The apparatus includes a first DC calibration unit for removing a DC offset from a signal, which is output from a Current-to-Voltage Converter (IVC), by using a first DC calibration value, a Variable Gain Amplifier (VGA) for amplifying the signal output from the IVC, a second DC calibration unit for removing a DC offset from a signal output from the VGA by using a second DC calibration value, a Low Pass Filter (LPF) for filtering the signal output from the VGA, a third DC calibration unit for removing a DC offset from a signal output from the LPF by using a third DC calibration value, and a controller for determining the first DC calibration value, the second DC calibration value and the third DC calibration value.