The two-sample problem refers to the comparison of two probability distributions via two independent samples. With high-dimensional data, such comparison is performed along a large number p of possibly correlated variables or outcomes. In genomics, for instance, the variables may represent gene expression levels for p locations, recorded for two (usually small) groups of individuals. In this paper we introduce TwoSampleTest.HD, a new R package to test for the equal distribution of the p outcomes. Specifically, TwoSampleTest.HD implements the tests recently proposed by (Cousido-Rocha, Uña-Álvarez, and Hart 2019) for the low sample size, large dimensional setting. These tests take the possible dependence among the p variables into account, and work for sample sizes as small as two. The tests are based on the distance between the empirical characteristic functions of the two samples, when averaged along the p locations. Different options to estimate the variance of the test statistic under dependence are allowed. The package TwoSampleTest.HD provides the user with individual permutation p-values too, so feature discovery is possible when the null hypothesis of equal distribution is rejected. We illustrate the usage of the package through the analysis of simulated and real data, where results provided by alternative approaches are considered for comparison purposes. In particular, benefits of the implemented tests relative to ordinary multiple comparison procedures are highlighted. Practical recommendations are given.Recently, Cousido-Rocha et al. ( 2019) overcame the aforementioned flaws by introducing a nonparametric omnibus test that, with focus on the marginal distributions, included the dependent case through mixing conditions (Doukhan, 1995). This type of dependence, being fairly general, has been frequently used in the goodness-of-fit testing literature; see for example Neumann and Paparoditis (2000) and Dehling et al. (2015). Mixing conditions imply that the dependence between the variables softens at distant locations. In genetics, for instance, this means that the correlation among expression levels of different genes lessens as the distance between the biological function of the genes increases, which is a flexible, realistic assumption for such applications.In this paper we introduce the TwoSampleTest.HD R package which implements the tests proposed in Cousido-Rocha et al. (2019) for testing the (global, or intersection) null hypothesis of equality of the p univariate marginals in the two populations. The basic test statistic is the L 2 -distance between the empirical characteristic functions pertaining to the two groups, when averaged along the p locations.