## 1 Introduction  
Nanoparticles (NPs), the building blocks of nanotechnology, are described as particles at the nanoscale measure 100 nm or below [1]. Due to their beneficial and unique physical, chemical, and mechanical qualities, NPs are widely used in a range of applications, including cosmetics, medications, energy, electronics, catalysis, wastewater treatment, food production, heavy metal adsorption, and agriculture [2]. Traditional physical and chemical technologies used to create NPs include labor-intensive, expensive, and destructive environmental processes [3]. To resolve these issues, a production technique called \"green synthesis\" has been developed, which differs from physical and chemical methods by being more environmentally friendly, economically viable, and instantly scalable for batch production. It also provides controlled growth, crystal growth, increased influence, increased stability, and uniform size [4, 5, 6, 7]. Many organisms, including _Ulva lactuca_, are recognized to have potential biological roles and activities, and facilitate such green nanotechnology [8; 9]. Algal biomass (either living or dried) has grown in popularity as a \"bio-nano-factory\" because of its rapid development, enhanced ability for metal and metal oxide accumulation and reduction, elevated biomass yield, growth without the need of fertilizers, and capacity to be harvested regularly [10; 11]. The green macroalgae, _U. lactuca_, which is common along Egypt's north coast, is a member of the class Ulvophyceae and the family Ulvacae. _U. lactuca_'s aqueous extract is rich in bioactive molecules, including ulvan polysaccharides, amides, pigments, proteins, amines, terpen, phenols, and alkaloids, all of which have a significant role in the stabilization and reduction of metal [12]. _U. lactuca_ extract has been used to create a wide variety of NPs with effective anticancer activity against the HCT-116 cell line. [PERSON] et al. [13] synthesized novel biogenic U-AgNPs, using _U. lactuca_ extract, which could serve as a potential novel therapeutic agent for cancer. For humans, selenium elements with anticancer and immunomodulatory properties are crucial and required. [PERSON]'s team showed that selenium NPs could greatly increase the 4T1 breast cancer tumor immune response in mice, and [PERSON]'s team discovered that selenium NPs (SeNPs) might limit prostate carcinoma cell growth partly through apoptosis caused by cystepsin [14]. It is noteworthy that the present study is the first to synthesize and test _U. lactuca_-mediated selenium NPs (USeNPs) for their anticancer activity against HepG2 carcinoma cells through the suppression effect on Epidermal Growth Factor Receptor (EGFR) since abnormal expression of EGFR is one of the therapeutic aims of cancer treatment. [PERSON] et al. [15] synthesized selenium particles but only tested them for their antibacterial activity. Extensive research on the EGFR signaling pathway has been motivated by the confirmation that the EGFR is strongly associated with tumor growth, progression, metastasis, and poor prognosis among patients [16; 17]. A surge in research focused on the design and synthesis of EGFR inhibitors has been sparked by mounting evidence that EGFR inhibitors offer significant promise in the therapy of malignancies, particularly non-small-cell lung cancer, pancreatic cancer, and liver cancer [18; 19; 20; 21; 22]. The design and synthesis of 14 compounds with EGFR inhibitory activity by [PERSON] et al. [23], along with computational exploration of the action mechanism, offered important clues for developing anticancer medicines based on EGFR inhibitors. SeNPs provide anticancer, immunomodulatory, and drug delivery effects. NPs with EGFR-targeted components have been shown to be more effective at inhibiting tumor cell growth, survival, metastasis, and angiogenesis [23]. Cancer poses a grave danger to human health and has significant social and economic repercussions.