Fluorescence molecular tomography (FMT) is a new type of medical imaging technology that can quantitatively reconstruct the three-dimensional distribution of fluorescent probes in vivo. Traditional Lp norm regularization techniques used in FMT reconstruction often face problems such as over-sparseness, over-smoothness, spatial discontinuity, and poor robustness. To address these problems, this paper proposes an adaptive parameter search elastic net (APSEN) method that is based on elastic net regularization, using weight parameters to combine the L1 and L2 norms. For the selection of elastic net weight parameters, this approach introduces the L0 norm of valid reconstruction results and the L2 norm of the residual vector, which are used to adjust the weight parameters adaptively. To verify the proposed method, a series of numerical simulation experiments were performed using digital mice with tumors as experimental subjects, and in vivo experiments of liver tumors were also conducted. The results showed that, compared with the state-of-the-art methods with different light source sizes or distances, Gaussian noise of 5%-25%, and the brute-force parameter search method, the APSEN method has better location accuracy, spatial resolution, fluorescence yield recovery ability, morphological characteristics, and robustness. Furthermore, the in vivo experiments demonstrated the applicability of APSEN for FMT.