Tunable diode laser absorption spectroscopy (TDLAS) technology is widely used in the industrial production and environmental pollution monitor due to its high resolution, high sensitivity and fast measuring speed. The second-harmonic signal of wavelength modulation spectroscopy (WMS) is often used as the detection signal for gas concentration inversion. The detection performance of TDLAS is closely related to the system parameters, such as the time constant of lock-in amplifier, scanning amplitude, scanning frequency, modulation amplitude and modulation frequency. The selection of each parameter in practical measurement is mostly according to the spectral line shape characteristics, in which method the relevance between each parameter is not considered completely. Since the signal sampling and processing affect the spectral line in the frequency domain, the mechanism of influence between parameters is interrelated. However, the influence of each parameter on the frequency domain of the signal was rarely researched. Aiming at this problem, the influence of modulation parameters on second harmonic signals was observed by experiment based on a certain theory in the present paper. The influence of each parameter on signal line shape, frequency characteristics and introduced noise was obtained when only one parameter was changed with all other parameters unchanged. Then the determinant of multi-parameter joint changes on spectral frequency band was analyzed and verified. Compared with traditional methods based on time-domain features, spectrum analysis from frequency characteristics has the advantages not only similar to the principle of spectrum signal acquisition, detection and processing, but also intuitive to get the influence of various parameters on the main frequency band and the attenuation trend of different frequencies signals. The basic selection method of each parameter was summarized based on spectral frequency characteristics. Firstly, the time constant and the scanning parameters should be reasonably set with the judgment criteria of the relationship between the spectral frequency band and the cutoff frequency, which is determined by the time constant of the lock-in amplifier. The appropriate time constants and scanning parameters should be set so that the signal frequency band is close to but not intersected with the cut-off frequency, the in-band components are not attenuated, and the out-band noise is maximally suppressed. Then, the modulation parameter should be determined to maximize the main frequency component amplitude of the spectrum on the basis of the function of lock-in amplifier and the spectrum signal noise ratio. Finally, the sampling rate should be determined according to the system requirements. When the sampling points of one period remain unchanged, the detection accuracy is relatively improved at low scanning frequency but the sampling time increases, on the contrary, the sampling speed increases and the detection accuracy decreases at a higher scanning frequency. The interrelated parameters should be adjusted simultaneously to reduce the influence of the hardware limit on the parameter optimal selection. In this paper, the optimal second harmonic signal can be obtained by parameter selection in the premise of sufficiently considering the system detection requirements and hardware condition limitations, which provided experimental basis and reference method of parameter optimization for the practical application of such technology.