Abstract Opuntia ficus-indica is used in animal feed but has a low protein content (above 4%) in comparison to high-quality forage (above 16%). It is necessary to develop technologies that improve the nutrimental value of Opuntia ficus-indica through the process of solid-state fermentation (SSF). Therefore, the objective of this study was to evaluate the changes in the chemical composition of Opuntia ficus-indica during the SSF with the yeast Kluyveromyces marxianus ITD00262. Kluyveromyces marxianus ITD00262 was grown in glucose, peptone, yeast (GPY) broth, at 28 °C and pH 4.8 for 12 h. Opuntia ficusindica was incubated in SSF at 28 °C without inoculation (T1) or inoculated with K. marxianus ITD00262 (T2). Fermented samples of Opuntia ficus-indica were dried, and the dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), lignin (LIGN) and in vitro dry matter digestibility (IVDMD) contents were ascertained. Data were analyzed with a completely randomized design with a factorial arrangement of 2×6. A decrease of 11% in DM was observed for T1 compared with T2 at 48 h of fermentation. A 300% increase in PC content was observed for T2 at 120 h of fermentation. The DMIVD was increased by 3%, whereas the values of NDF and ADF decreased by 18% in T2. According to our results, it is confirmed that the use of K. marxianus in the SSF of Opuntia ficus-indica has a positive effect and improves the nutrimental quality of this forage.