Investigation of unsteady mixing and combustion effects presents a significant interest in the design and optimization of direct injection spark-ignition (DISI) engines. The main attention focused on the analysis of impact of in-cylinder velocity cyclic variations on mixing and combustion processes. For this purpose multi-cycle large eddy simulation (LES) of the flow, mixing and combustion have been done in a realistic four-stroke internal combustion (IC) engine. The LES method has been used to simulate up to 50 consecutive engine cycles. The paper summarizes the main findings regarding cycle-to-cycle variations of in-cylinder velocity flow filed as well as mixing processes. Then the unsteady effects of spray combustion processes are discussed in details.