Photoacoustic imaging (PAI) has been applied to many biomedical applications over the past decades. However, the received PA signal usually suffers from poor signal-to-noise ratio (SNR). Conventional solution of employing higher-power laser, or doing long-time signal averaging, may raise the system cost, time consumption, and tissue damage. Another strategy is de-noising algorithm design. In this paper, we propose a new de-noising method, termed gradient-based adaptive wavelet de-noising, which sets the energy gradient mutation point of low-frequency wavelet components as the threshold. We conducted simulation, ex vivo and in vivo experiments to validate the performance of the algorithm. The quality of de-noised PA image/signal by our proposed algorithm has improved by 20%-40%, in comparison to the traditional signal denoising algorithms, which produces better contrast and clearer details. The proposed de-noising method provides potential to improve the SNR of PA signal under single-shot low-power laser illumination for biomedical applications in vivo.