We have studied the double effects of anisotropic strain and temperature on the dissolution behavior of hydrogen (H) in tungsten (W) by using first-principles calculation combined with thermodynamic model. The strain and temperature effects are reflected by uniaxial/biaxial strain loading and vibrational Helmholtz free energy, respectively. We calculated the dissolution energy of the H atom at four different interstitial sites of TIS(1), TIS(2), OIS(1) and OIS(2). For TIS(2), OIS(1) and OIS(2), the dissolution energy of H changes monotonically as the biaxial strain rises from −5% to 5%. However, the dissolution ability of H at TIS(1) can be promoted by employing either compressive or tensile biaxial strain. There are more interesting results, the temperature-dependent dissolution energy of H at TIS(1) shows a significant decrease with the compressive biaxial strain loading, but this phenomenon does not occur at other three positions, i.e., TIS(2), OIS(1) and OIS(2). Besides, with the same anisotropic strain loading, the dissolution energy of H for all four kinds of positions increase as the temperature rises from 300 to 1800 K, which is mainly originated from the contribution of the vibrational Helmholtz free energy. Our results indicate that H atoms are more easily to accumulate in the anisotropic strain enrichment region in W as the temperature rises, which will make it more easier to form H bubbles in W.