The friction characteristic parameters of cotton stalks are important basic physical parameters required to establish the crushing mechanics model and study the separation machinery of film residue mixtures. In this paper, the friction characteristics of cotton stalks were studied using response surface methodology, and the influence of the variation in contact materials, sampling location, and moisture content on the static sliding friction coefficient (μs) and stable static rolling angle (φs) were analyzed. The results show that the contact materials, sampling location, and moisture content significantly influence the μs and φs. When the contact material is cotton stalk bark, the μs and φs values of cotton stalks are maximum. When the sampling location of the cotton stalk changes from top to bottom, the μs increases and φs decreases, respectively, while the moisture content has an opposite influence on the μs and the φs. The model coefficient of the μs and the φs indicates that the influencing factors have a high degree of explanation for the influence on the μs and φs. This study on the friction characteristics of cotton stalks can provide theoretical references and basic parameters for the separation technology research and equipment development of film residue mixtures.