The role of perioperative pain management techniques on immune functions in patients with malignancies is still poorly understood. Although the suppression of cellular and humoral immune response in carcinoma patients is a subject of great scientific interest, we know very little about the changes in innate immunity (natural killer T cells-NKT cells, regulatory T cells-Tregs) following tumor growth, as well as in acquired immunity and cytotoxic functions of NK cells in these patients undergoing surgery and the involvement of different perioperative analgesia techniques. Immune compromise could affect the healing processes, postoperative infections and rate and size of tumor metastases disseminated during operation and may be associated with increased risk of mortality immunosuppression is also a result of perioperative psychological and physiological stress induced by the mechanisms closely related to hypothalamus-pituitary-adrenocortical axis, sympathetic nervous system, cytokines, opioids and T cell signal molecule. Furthermore, peripheral and central immune reaction play a key role in hyperalgesia and allodynia, as a consequence of releasing proinflammatory cytokines (PIC) from activated microglia and astrocytes.Release of PIC causes the augmented secretion of excitatory neurotransmitters from synaptic nerves of primary afferent neuron, representing PIC as very important mediators of enhanced pain in the periphery and in the central nervous system. These findings emphasise that perioperative pain management in patients with malignancies is significant to attenuate developed serious immune suppression mediated by the complicated network of neuro-immuno-endocrine interactions caused by the primary disease accompanied with exogenous and endogenous stimuli.