In this paper, we study the Newton polytopes of F -polynomials in totally sign-skewsymmetric cluster algebras and generalize them to a larger set consisting of polytopes N h associated to vectors h ∈ Z n as well as P consisting of polytope functions ρ h corresponding to N h .The main contribution contains that (i) obtaining a recurrence construction of the Laurent expression of a cluster variable in a cluster from its g-vector; (ii) proving the subset P of P is a strongly positive basis of U (A) consisting of certain universally indecomposable Laurent polynomials, which is called as the polytope basis; (iii) constructing some explicit maps among corresponding F -polynomials, g-vectors and d-vectors to characterize their relationship.As an application of (i), we give an affirmation to the positivity conjecture of cluster variables in a totally sign-skew-symmetric cluster algebra, which in particular provides a new method different from that given in [12] to present the positivity of cluster variables in the skew-symmetrizable case.As another application, a conjecture on Newton polytopes posed by Fei is answered affirmatively.For (ii), we know that in rank 2 case, P coincides with the greedy basis introduced by Lee, Li and Zelevinsky. Hence, we can regard P as a natural generalization of the greedy basis in general rank.As an application of (iii), the positivity of denominator vectors associated to non-initial cluster variables, which was first come up as a conjecture in [10], is proved in a totally sign-skew-symmetric cluster algebra.