We evaluated the effects of supplementing direct-fed microbials (DFM), containing Bacillus licheniformis and Bacillus subtilis, on performance, rumen morphometrics, intestinal gene expression, and blood and fecal parameters in finishing bulls. Nellore x Angus bulls (n = 144; initial BW = 401 +/- 45.5 kg) were distributed at random in 36 pens (4 bulls/pen and 18 pens/treatment), following a completely randomized design. A ground corn-based finishing diet was offered for ad libitum intake twice a day for 84 d, containing the following treatments: 1) control (without DFM); 2) DFM (B. licheniformis and B. subtilis) at 6.4 x 109 CFU (2 g) per animal. The data were analyzed using the MIXED procedure of SAS, with a pen representing an experimental unit, the fixed effect of the treatment, and the random effect of pen nested within the treatment. For fecal parameters (two collections made), the collection effect and its interaction with the treatment were included in the model. Bulls that received the DFM had a decreased dry matter intake (P <= 0.01), did not differ in average daily gain (2.05 kg; P = 0.39), and had a 6% improvement in gain:feed (P = 0.05). The other performance variables, final BW, hot carcass weight, and hot carcass yield, did not differ (P > 0.10). Plasma urea-N concentration decreased by 6.2% (P = 0.02) in the bulls that received DFM. Glucose, haptoglobin, and lipopolysaccharides were not different between treatments (P > 0.10). Ruminal morphometrics were not affected by the treatment (P > 0.10). The use of DFM tended to reduce fecal starch (P = 0.10). At slaughter, bulls fed DFM had an increased duodenal gene expression of tryptophan hydroxylase-1 (P = 0.02) and of superoxide dismutase-1 (P = 0.03). Overall, supplementation with DFM based on B. licheniformis and B. subtilis to Nellore x Angus bulls in the finishing phase decreased dry matter intake, did not influence ADG, improved gain:feed, and increased the expression of genes important for duodenal function. One of the main alternatives of additives to modulate the microbial population in the gastrointestinal tract (GIT), especially in the intestine, is the use of direct-fed microbials (DFM). This class of additives comprises all the feed products that contain a live or naturally occurring source of microorganism. The inclusion of DFM in diets of ruminants in the finishing phase may improve gain:feed by modifying the composition of the microbial community in the GIT to bring about a better symbiotic relationship with the host. These effects may be achieved with the use of Bacillus spp. bacteria, such as Bacillus licheniformis and Bacillus subtilis. Mixtures of these bacteria are able to foster positive effects in the finishing phase of beef cattle fed high-energy diets, which reinforces the need for studies that examine the effects and mechanisms of these species. In this study, feedlot Nellore x Angus bulls that received a DFM composed of B. licheniformis and B. subtilis had decreased dry matter intake, no influence on average daily gain, improved gain:feed, and an increase in expression of genes important for duodenal function.