Quantum cascade laser (QCL) plays an important role in mid-infrared detection because of the high output power and wide coverage range. However, due to the fluctuation of laser wavelength caused by the sensitivity of the laser to changes in the external environment, the peak-to-peak frequency drift is as high as 180 MHz within the observed time of 400 s, which affects the performance of the QCL to some extent and reduces the accuracy of molecular spectral detection. Frequency locking has been widely applied to the mid-infrared areas. In this paper, a QCL frequency locking system based on gas absorption was developed. Taking 5.3 μm QCL as an example, the laser frequency is locked to the absorption peak of nitric oxide (NO) molecule at 1 875.812 8 cm-1 by modulating laser wavelength. The principle of error signal generation was introduced, and the advantages of using the third harmonics as an error signal for frequency locking were analyzed. The NO absorption signal with a high signal-to-noise ratio (SNR) was obtained using a NO absorption cell with a length of 30 cm. The conversion coefficient between the third harmonic voltage and the laser frequency was calibrated. The locking process was introduced in detail and explored the significance of proportional, integral, differential parameters of the feedback loop during the locking process, and the locking parameters had been given in detail. Disturbing the locking system, with the recovery time better than 40 ms demonstrate that the locking system can respond quickly and remain stable against external disturbances. In addition, the stability of the frequency locking system was also verified by the fluctuation of the error signal with the voltage-frequency conversion coefficient. A frequency drift better than 673 kHz (1σ, 10 ms integration time) was achieved. The Allan variance analysis results show that when the integrated time is extended to 100 s, the frequency drift is lower than 4.5 kHz (corresponding to stability of 8×10-11), effectively improving the laser frequencys long-term stability. This method of directly modulating laser frequency without an external modulator simplified the system and improved the stability of the optical detection system.